J Pharmacobiodyn, 1992 Sep, 15(9), 481 - 9 Mechanisms of intestinal absorption of the antibiotic, fosfomycin, in brush-border membrane vesicles in rabbits and humans; Ishizawa T et al.; In order to clarify the mechanism of intestinal absorption of an antibiotic, fosfomycin (FOM), the uptakes of FOM by rabbit and human small intestinal brush-border membrane vesicles (BBMV) were studied . The initial uptake of FOM by BBMV at 15 s was saturable at a higher concentration of FOM . The kinetic parameters at 37 degrees C of the saturable uptake expressed by the Michaelis-Menten equation were Kt = 5.17 mM and Jmax = 3.88 nmol/15 s/mg protein for rabbits, and Kt = 4.03 mM and Jmax = 1.90 nmol/15 s/mg protein for humans . The most efficient uptake was observed in the presence of both inward-directed Na(+)- and H(+)-gradients in both mammals . The uptake of FOM was inhibited by inorganic phosphate, FOM glycol which is a degradation product of FOM in the gastric juice and specific inhibitors of phosphate transport such as arsenate and phosphonoacetic acid . These findings confirmed that FOM absorption from rabbit and human small intestines is associated with the phosphate transport system . These transport phenomena of FOM are in close agreement with those obtained previously in rat BBMV studies . Judging from the results obtained for three mammalian species, rat, rabbit and human, it was concluded that carrier-mediated transport via the phosphate transport system is a very important pathway of intestinal absorption of FOM. East Afr Med J, 1992 Sep, 69(9), 490 - 3 Post-operative management of pterygium in Jos, Nigeria--comparison of antibiotics, steroids and opticrom; Ibechukwu BI; Eighty six patients with a total of 125 pterygium-affected eyes were treated by surgical excision and one of three post-operative topical, medical adjuvants--antibiotics, steroids or Opticrom--to try and control the recurrence rate . The result showed that opticrom 2% ophthalmic drops was most effective in controlling pterygium recurrence . Steroids proved more effective than antibiotics. J Mol Biol, 1992 Aug 20, 226(4), 935 - 41 Non-competitive inhibition of group I intron RNA self-splicing by aminoglycoside antibiotics; von Ahsen U et al.; Aminoglycoside antibiotics inhibit self-splicing of group I intron RNA in vitro at concentrations as low as 10(-6) M . The sites of interaction and the mechanism of inhibition have yet to be determined . A comparative study of inhibition by different 2-deoxystreptamine analogues reveals structural features of the aminoglycoside antibiotics required for their interaction and effect on group I introns . Complete antibiotic inhibition of the two steps of splicing was not reversed at high concentrations of guanosine, indicating a non-competitive inhibition . A mutant group I intron in which the conserved guanosine nucleotide of the G-binding site had been replaced by an adenosine, was sensitive to the antibiotics providing direct evidence that the antibiotics do not interact with the G-binding site in the same way as the guanine base . In addition kinetic analyses of the self-splicing process in the presence of antibiotic inhibitors supported a non-competitive mechanism of the mixed type for inhibition of the ribozyme. Am J Ophthalmol, 1992 Aug 15, 114(2), 212 - 5 The solubility of antibiotic and corticosteroid combinations; Lee BL et al.; The use of collagen shields soaked in various combinations of medications has been advocated to enhance drug delivery to the cornea . Recently, severe corneal toxicity associated with aggregate formation in mixtures of gentamicin and methylprednisolone prompted our study of the effect of drug concentration, pH, and temperature on the solubility of several antibiotic and corticosteroid formulations commonly used to treat ocular disease . Selected combinations of cefazolin, vancomycin, tobramycin, gentamicin, methylprednisolone, and dexamethasone were evaluated . Mixtures of tobramycin and vancomycin produced no precipitates, but many spheroid aggregates were seen when methylprednisolone and gentamicin were combined . Although the effects of precipitate formation on drug bioavailability and toxicity have not been fully determined, until such information is available, the use of combinations of drugs that remain in solution during administration is recommended. Proc Natl Acad Sci U S A, 1992 Aug 15, 89(16), 7654 - 8 The antibiotic azatyrosine suppresses progesterone or {Val12}p21 Ha-ras/insulin-like growth factor I-induced germinal vesicle breakdown and tyrosine phosphorylation of Xenopus mitogen-activated protein kinase in oocytes; Campa MJ et al.; The antibiotic azatyrosine {DL-3-(5-hydroxy-2-pyridyl)alanine} suppressed meiotic maturation in oocytes induced by progesterone or the combination of {Val12}p21Ha-ras microinjection and insulin-like growth factor I . The suppression was dose-dependent in the range of 20-250 microM azatyrosine . In addition, azatyrosine blocked the tyrosine phosphorylation of Xp42, a member of the mitogen-activated protein kinase family, after progesterone or {Val12}p21Ha-ras/insulin-like growth factor I stimulation . Activation of maturation-promoting factor, as shown by a decrease in the tyrosine phosphorylation of the Xenopus homolog of p34cdc2, was also suppressed by azatyrosine . Azatyrosine had no effect in vivo or in vitro on the growth factor-induced autophosphorylation of the oocyte insulin-like growth factor I receptor . Azatyrosine has been shown by others {Shindo-Okada, N., Makabe, O., Nagahara, H . & Nishimura, S . (1989) Mol . Carcinog . 2, 159-167} to inhibit the growth of ras-transformed cells without affecting that of nontransformed cells . In oocytes, the antibiotic exerts an inhibitory action on both a ras-dependent and a ras-independent pathway . Lack of an effect of azatyrosine on germinal vesicle breakdown induced by the microinjection of an extract from mature oocytes, however, suggests that azatryosine is acting upstream of maturation-promoting factor activation. J Chromatogr, 1992 Aug 14, 606(2), 229 - 35 Determination of aminoglycoside antibiotics in pharmaceuticals by capillary zone electrophoresis with indirect UV detection coupled with micellar electrokinetic capillary chromatography; Ackermans MT et al.; Aminoglycoside antibiotics can be determined by capillary zone electrophoresis (CZE) with indirect UV detection in the anionic mode with a reversed electroosmotic flow (EOF) by addition of FC 135 to the background electrolyte . The effective mobilities of thirteen aminoglycoside antibiotics were determined as a function of pH . Applying CZE with indirect UV detection in the anionic mode and reversed EOF coupled with micellar electrokinetic capillary chromatography with the cationic surfactant cetyltrimethylammonium bromide, both neutral and charged antibiotics can be determined in combined pharmaceuticals . As an example, neomycin and hydrocortisone were determined in Otosporin eardrops. Pharmacoeconomics, 1992 Sep, 2(3), 238 - 44 Consumption of antibiotics in Sweden, 1975 to 1992: pharmacoeconomic and clinical aspects; Norrby SR; Using official statistics for the consumption of antibiotics in Sweden during the period 1975 to 1991, the pharmacoeconomic consequences were analysed . An increase of more than 25% in Swedish consumption of antibiotics during the study period was found . There is no obvious clinical explanation; indeed, improved hospital hygiene as well as decreased frequencies of some common bacterial infections should have resulted in a decrease in total consumption . Overconsumption was most marked for oral antibiotics . In 1991 the most often used antibiotic, phenoxymethylpenicillin, was given in about 20 million defined daily doses (DDD), corresponding to 2.4 DDDs per member of the population per year . From a pharmacoeconomic viewpoint, this overconsumption is acceptable because the drug has a low price and causes a minimum of severe adverse reactions . More serious is the marked misuse of tetracyclines (12 million DDDs in 1991) and macrolides (5.3 million DDDs in 1991), with which adverse reactions are more common, and where the high consumption has led to increasing frequencies of resistance among common bacterial pathogens . This emergent resistance often leads to a need to use newer more expensive antibiotics, in addition to the costs resulting from therapeutic failures of the initial treatment . Of the parenteral antibiotics, the cephalosporins, particularly cefuroxime, dominate in Sweden . The introduction of 'diagnosis-related groups' (DRGs) for reimbursement of hospitals for in-patient care is likely to result in the development of antibiotic use in 'intensive home care' as has occurred in the US.(ABSTRACT TRUNCATED AT 250 WORDS) Biochem Pharmacol, 1992 Aug 4, 44(3), 539 - 45 Polyene macrolide antibiotics: indirect stimulation of the Na+/H+ exchanger of BALB/c B lymphoid cell line, A20; Cybulska B et al.; The fluorescent pH probe, 2'-7'-bis (carboxyethyl) 5-carboxyfluorescein, was used to follow changes in internal pH (pHi) induced by aromatic polyene antibiotics in the BALB/c lymphoid cell line A20 . The antibiotics studied were vacidin, which contains a free carboxylic group in the position C18 of the macrolide ring, and vacidin glycyl methyl ester and perimycin, which are without free carboxylic groups . Although all of them induced transmembrane Na+ and K+ movements, only vacidin had protonophoric activity, as previously demonstrated for red blood cells {Cybulska B et al., Biochem Pharmacol 38: 1755-1762, 1989} . However, with all three antibiotics, pHi changes were observed in A20 cells . It was demonstrated that the transmembrane H+ movements resulted to different degrees, principally in the case of perimycin and vacidin glycyl methyl ester, or partially in the case of vacidin, from the stimulation of the Na+/H+ exchanger by the induced Na+ permeability . The non-aromatic polyene antibiotic amphotericin B had a low ability to increase proton permeability. Eur J Pharmacol, 1992 Aug 3, 226(4), 287 - 96 Magainin 2, a natural antibiotic from frog skin, forms ion channels in lipid bilayer membranes; Cruciani RA et al.; We have examined the ion channel forming properties of magainin 2 by incorporating the peptide into artificial lipid bilayers held under voltage clamp . Magainin 2 increased lipid bilayer conductance in a concentration dependent manner with a Hill coefficient of 1.7 . The magainin 2 conductance was selective for monovalent cations over anions with a ratio of 5:1 and had both voltage-sensitive and -insensitive components . Two structurally related but antibiotically less potent analogues, magainin 1 and Z-12, also increased lipid bilayer conductance with a similar ion selectivity but these peptides were less potent than magainin 2 . We propose that the weak cation selectivity of the magainin channels can be accounted for by the inclusion of negatively charged lipids in the channel complex and suggest two possible structures for such a channel . The ionophoric properties of these peptides are likely to be proximal to their antibiotic activities. Surg Gynecol Obstet, 1992 Aug, 175(2), 113 - 4 A prospective randomized double blind study of perioperative antibiotic use in the grafting of ulcers of the lower extremity; Bizer LS et al.; We conducted a prospective, randomized, double blind study of the use of a perioperative antibiotic in the skin grafting of arterial and venous ulcers of the lower extremity . Ninety-four patients were randomized and 90 were available for analysis . There was no statistically significant difference in graft "take" or incidence of recipient site infection in the antibiotic versus the no antibiotic group. Pediatr Emerg Care, 1992 Aug, 8(4), 194 - 9 Prophylactic oral antibiotics for low-risk dog bite wounds; Dire DJ et al.; The use of prophylactic antibiotics in the initial treatment of noninfected dog bite wounds is controversial . All patients with noninfected dog bite wounds who presented to our emergency department (ED) over a two-year period were considered for entry into a randomized prospective study . Patients were excluded from the study if they had any high-risk criteria for infection: puncture wounds, hand or foot wounds, wounds greater than 12 hours old, a history of immunocompromising disorders, or the use of immunosuppressive drugs . Patients in the antibiotic group (n = 89) were treated with local wound care and given either dicloxacillin, cephalexin, or erythromycin orally for seven days . Patients in the control group (n = 96) received local wound care only . All patients had their wounds irrigated with a 1% povidone-iodine solution and debrided and sutured if clinically indicated . All patients were subsequently reevaluated for clinical signs of wound infection . The groups were similar in age, sex, time of delay in seeking treatment, anatomic sites of wounds, depths and types of wounds, and number of wounds requiring suturing . The wound infection rates for the antibiotic and control groups were 1.1 and 5.1%, respectively . This difference was not significant (P = 0.212) . There were 36 wounds in the antibiotic group and 37 wounds in the control group that were full thickness . The infection rates for these wounds were 2.8 and 13.5%, respectively . This was not statistically significant (P = 0.132) . This study suggests that prophylactic oral antibiotics in low-risk dog bite wounds are not indicated. Clin Orthop, 1992 Aug, (281), 216 - 23 Treatment of acutely infected arthroplasties with incision, drainage, and local antibiotics delivered via an implantable pump; Perry CR et al.; Twelve patients with acutely (symptomatic less than ten weeks) infected arthroplasties were treated with minimal debridement and intraarticular antibiotic, amikacin, delivered via an implantable pump . The infection was suppressed in ten cases . Intraarticular levels of amikacin were obtained in eight cases . These levels ranged from greater than 150 micrograms/ml to 1688 micrograms/ml . The systemic level of amikacin remained below 10 micrograms/ml in all but one case . Duration of hospitalization averaged 19 days . There were no significant toxic side effects to amikacin. Can J Microbiol, 1992 Aug, 38(8), 769 - 73 Sporulation of Streptomyces antibioticus ETHZ 7451 in submerged culture; Novella IS et al.; Streptomyces antibioticus ETHZ 7451 formed spores in cultures grown in a liquid medium from either a spore or a mycelium inoculum . The spores formed were similar to those formed on surface-grown cultures, except for reduced heat resistance . Both types of spores were sensitive to lysozyme, which is unusual for Streptomyces spores . Glucose and other carbon sources, which promoted different growth rates, did not affect sporulation efficiency . Nitrogen sources, such as casamino acids, that allowed high growth rates suppressed the sporulation . A remarkable repression was also observed in media with some nitrogen sources that promoted noticeably lower growth rates . In permissive media, with nitrogen sources that permitted relatively high growth rates, sporulation was conditioned to the consumption of ammonium in the medium, but not to that of other nitrogen sources, such as asparagine . Phosphate did not show a repressive effect on sporulation in the assayed conditions. Antibiot Khimioter, 1992 Aug, 37(8), 35 - 7 {Use of a physiological model of gentamicin pharmacokinetics for individual dosage of the antibiotic}; Manuilov KK et al.; A new approach to fixing the initial doses of gentamicin (GM) for its intramuscular administration (the most commonly used anyway) is discussed . The approach is based on the physiological model reproducing the individual patterns of GM concentration change in patient's blood . Such parameters of the model as blood flow velocity and actual average volume of specific tissues as well as the tissue to the blood partition coefficient (Kp) are constant . They were used to calculate the volume of distribution in the body specific organs (Vs) . The apparent distribution volume (Vd) and total clearance (Cl) are individual parameters . The Vd value was calculated individually for every particular patient depending on the body weight by the known equations . The difference between Vd and Vs was used to calculate the individual Kp for the organs and tissues which were not specially examined . When calculating Cl of GM, the patient's sex, age, weight and creatinine concentrations were taken into account . To evaluate the local velocity of blood flow after antibiotic intramuscular administration, it was important to consider the patient's sex and age . The approach was used to reproduce the individual patterns of GM concentration change after the initial administration of the antibiotic, 80 mg, to 19 male patients (age range, 21 to 73 years; weight range, 50 to 94 kg; blood creatinine concentration, 0.4 to 1.6 mg/dl) . The GM concentrations attained with the use of the model were afterwards compared to the data on FPIA . (TDx, Abbott) by measuring the GM concentrations in the blood of the patients 0.5, 1, 5 and 7 hours after the administration.(ABSTRACT TRUNCATED AT 250 WORDS) Antibiot Khimioter, 1992 Aug, 37(8), 29 - 31 {Search for inhibitors of West Nile virus among antibiotics}; Azarova IA et al.; The activity of 24 antibiotics was studied in treatment of albino mice with experimental encephalitis caused by West Nile virus . The antiviral activity of gentamicin and kanamycin was stated . The survival rate of the animals 19 . contaminated with 10-100 LD50 of the West Nile virus and treated parenterally with gentamicin in a dose of 80 to 400 micrograms/mouse was higher than that in the controls by 29.5 to 100 per cent and depended on the drug regimen . The efficacy of kanamycin was lower . The chemotherapeutic indices of gentamicin and kanamycin amounted to 100 and 10, respectively . Since there are no schemes for chemotherapy of the infection caused by the West Nile virus and the respective vaccines are not available the use of the antibiotics and gentamicin in particular appears to be promising in the disease prevention and treatment. Antibiot Khimioter, 1992 Aug, 37(8), 27 - 9 {Isolation and evaluation of the structure of the new anthracycline antibiotics rubomycins F and H}; Fomicheva EV et al.; The rubomycin complex produced by Streptomyces coeruleorubidus 4-157 was studied and the two novel anthracyclines i.e . rubomycins F and H were isolated . The study of the physicochemical properties of the novel antibiotics in comparison with rubomycin C (daunomycin) and the specially prepared 3'-N-carbmethoxyrubomycin C showed that rubomycin F was 3'-N-carbethoxydaunomycin and rubomycin H was 3'-N-carbmethoxydaunomycin . Therefore, rubomycins F and H are novel representatives of natural anthracyclines undescribed previously. Scand J Dent Res, 1992 Aug, 100(4), 232 - 5 Antibiotic prescribing practices among Norwegian dentists; Preus HR et al.; There is scarce information on antibiotics prescription habits among dentists in general . The present investigation was undertaken to study some patterns of antibiotics prescription among Norwegian dentists . A total of 459 dentists (approximately 10% of Norwegian dentists) were randomly selected, and to each was mailed a letter describing the survey, accompanied by a questionnaire about age, type of practice, educational background and pattern of prescription of antibiotics . 78% of the dentists responded to these questions . The results indicate that during a typical week, 32% did not prescribe antibiotics, whereas 5% wrote greater than 5 prescriptions . The mean weekly number of prescriptions per dentist was 2.04 . Periodontists and oral surgeons prescribed antibiotics significantly more often than did general practitioners and other disciplines . In addition, those with research and/or teaching experience seemed to prescribe significantly more often than those without . More than 1/3 of the sample indicated that they may prescribe antibiotics when treating periodontal diseases . Compared with other disciplines, periodontists prescribed such drugs significantly more often when treating periodontitis, but significantly less often in acute gingivitis, stomatitis and herpes simplex infections . Moreover, 22% of the dentists might prescribe antibiotics when the patient is in pain, 73 and 38% in cases of abscesses with or without generalized malaise, 2.5% in endodontic therapy, 60% to prevent general complications, and 68% for prophylactic use if the patient revealed a history of endocarditis . Norwegian dentists are somewhat restrictive in their prescription of antibiotics, but they mostly prescribe the correct drugs for the different conditions. J Biomed Mater Res, 1992 Aug, 26(8), 1053 - 64 Synthesis of antibiotic-loaded hydroxyapatite beads and in vitro drug release testing; Yamamura K et al.; Various forms of hydroxyapatite (HAP) materials have been developed for use as bone grafts . Since the risk of local infection is associated with surgery, it seems reasonable to incorporate drugs such as antibiotics into implant materials . We therefore investigated the characteristics of drug incorporation into a spherical porous HAP bead (diameter = 8.48 mm, bulk porosity = 0.439) and its in vitro release behavior . Cefotiam (CTM) was used as a model antibiotic . Because of nonuniform pore distribution in the bead, distribution of CTM was estimated from the amounts of CTM experimentally determined at three different sites: the surface, halfway to the center, and the center of the beads . The results indicated that 90% of the drug was incorporated in the concentric outer 0.387 (radius = 1) section of the bead . CTM was released with a short lag time when the dry HAP bead was placed in water . Incorporation of CTM with egg phosphatidylcholine eliminated initial lag time and decreased the release rate of the drug from the bead . The lipid load was useful in controlling the release of CTM from the beads . In addition, to protect relatively unstable drugs from humidity and avoid contamination of drug-incorporated HAP beads an apparatus was designed with which the beads could be enclosed in vials in vacuo and under aseptic conditions on a bench-scale basis. Indian J Biochem Biophys, 1992 Aug, 29(4), 371 - 4 Role of antibiotics in lipid peroxidation; Vijayalekshmy KS et al.; Alterations in the levels of lipid peroxides, superoxide dismutase, catalase, glutathione, free fatty acid and serum ceruloplasmin were studied in rats fed with high fat cholesterol diet administered different antibiotics, viz . ampicillin, tetracycline, streptomycin, chloramphenicol and cephalosporin . The concentrations of lipid peroxides, glutathione, free fatty acid decreased in most of the tissues, except in tetracycline, streptomycin and cephalosporin treated rats . The changes observed in the activities of superoxide dismutase and catalase in the liver and kidney of these antibiotics administered groups also are in accordance with the changes in lipid peroxides . The results show that the tetracycline is hepatotoxic and nephrotoxic, while cephalosporin and streptomycin are nephrotoxic. Aliment Pharmacol Ther, 1992 Aug, 6(4), 495 - 502 Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin; Langholz E et al.; Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin . Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients . Eight Crohn's disease patients were included . Fusidic acid was administered orally in a dose of 500 mg t.d.s . and the treatment was planned to last 8 weeks . The disease activity was primarily measured by a modified individual grading score . Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks . There were no serious clinical side effects, but dose reduction was required in two patients because of nausea . Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment . All reversed to pre-treatment levels after cessation of treatment . The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective . Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated. Biol Chem Hoppe Seyler, 1992 Aug, 373(8), 675 - 83 Secondary fungal metabolites and their biological activities, II . Occurrence of antibiotic compounds in cultures of Armillaria ostoyae growing in the presence of an antagonistic fungus or host plant cells; Peipp H et al.; We found that in the presence of host plant cells or some antagonistic fungi, the highly forest-pathogenic basidiomycete Armillaria ostoyae is strongly stimulated to produce a series of toxic secondary metabolites which are capable of inhibiting the growth of the antagonist or of killing the plant cells still before cell contact . The chemical structures of the metabolites have been identified, of which two of them are new compounds . The time dependence and sites of synthesis in the mycelium have been determined in order to lay the foundation for future studies concerning the induction mechanism for the synthesis of the toxins. J Antibiot (Tokyo), 1992 Aug, 45(8), 1295 - 302 Immunomodulating properties of prodigiosin 25-C, an antibiotic which preferentially suppresses induction of cytotoxic T cells; Tsuji RF et al.; An antibiotic, prodigiosin 25-C, preferentially suppresses cytotoxic T lymphocytes (CTL) without affecting antibody production . Here, we investigated the effect of prodigiosin 25-C on delayed-type hypersensitivity (DTH), graft versus host reaction (GvHR) and allogeneic skin graft rejection . DTH reactions were markedly inhibited by ip treatment of the mice with prodigiosin 25-C . Cell transfer experiments indicated that prodigiosin 25-C exerted its suppressive effect on the late efferent phase rather than on the induction phase of DTH . Prodigiosin 25-C suppressed induction of anti-host CTL when GvHR was induced by iv inoculating splenocytes of parental C57BL/6 mice to adult unirradiated BDF1 mice . It had little effect on GvHR-induced splenomegaly observed 2 weeks after the inoculation, but significantly delayed the subsidence of splenomegaly as revealed 8 weeks later, suggesting that suppression of CTL converts immunosuppressive GvHR to immunostimulative one as reported by G . M . Shearer . However, reduction of interleukin-2 (IL-2) production and mitogen responses induced by GvHR were not rescued by prodigiosin 25-C treatment . Prodigiosin 25-C moderately prolonged survival of major histocompatibility (MHC)-mismatched skin grafts . Since the mode of action of prodigiosin 25-C is distinct from those of cyclosporin A and FK506, these results demonstrate potential usefulness of the antibiotic for a supplementary immunosuppressant. J Antibiot (Tokyo), 1992 Aug, 45(8), 1255 - 67 Anthracycline metabolites from baumycin-producing Streptomyces sp . D788 . I . Isolation of antibiotic-blocked mutants and their characterization; Yoshimoto A et al.; Biosynthetically blocked mutants were obtained from a baumycin-producing Streptomyces sp . D788 newly isolated from soil . The first mutant isolated was a baumycin-negative but daunorubicin-accumulating mutant with a loss of 4'-substitution activity, from which all other blocked mutants were successively derived . These included a known 11-deoxydaunorubicin-producing mutant and several new types of mutants which produced mainly 10-carboxy-13-deoxocarminomycin, 10-methoxycarbonyl-13-deoxocarminomycin, their 11-deoxy derivatives or a precursor aglycone, respectively . In this paper, all the anthracycline components produced by the parent strain and its two known blocked mutants, a daunorubicin producer and a 11-deoxydaunorubicin producer, are also determined by HPLC and five new components are isolated . Cytotoxicities in vitro of all the components against L1210 cell culture are also described. J Antibiot (Tokyo), 1992 Aug, 45(8), 1250 - 4 Kedarcidin, a new chromoprotein antitumor antibiotic . II . Isolation, purification and physico-chemical properties; Hofstead SJ et al.; Kedarcidin, a new chromoprotein antitumor antibiotic, was isolated from the culture broth of a novel actinomycete strain L585-6 (ATCC 53650) . The antibiotic was recovered from the culture filtrate by adsorption to QAE ion exchanger and purified by successive application of gel filtration and ion exchange chromatography with Sephadex G-50 and DEAE-Sephadex, respectively . Kedarcidin is an acidic complex (pI 3.65) with an apparent molecular weight of 12,400 . The complex consists of a highly unstable, solvent extractable chromophore and a water soluble peptide . The apoprotein is a single chain polypeptide of 114 residues. J Antibiot (Tokyo), 1992 Aug, 45(8), 1239 - 49 Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces roseiscleroticus . Production, isolation, structure and biological activity; Ohkuma H et al.; Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and antitumor antibiotic, sultriecin . It exhibited in vitro antifungal activity and potent in vivo antitumor activity against P388 and L1210 leukemias, and B16 melanoma . Sultriecin is composed of several unique structural units; a conjugated triene, an alpha,beta-unsaturated delta-lactone, and a sulfate functionality. J Antibiot (Tokyo), 1992 Aug, 45(8), 1231 - 8 Isolation and structure elucidation of new antibiotics related to angolamycin; Kadar-Pauncz J et al.; Angolamycin (1) and two novel analogues (2 and 3) were isolated from the culture broth of a Streptomyces strain . NMR and MS analysis proved that 2 is the 18-dihydro-, while 3 is the 18-deoxo-18-dihydro derivative of angolamycin . Full experimental assignment of the 1H and the 13C NMR spectra of these compounds was obtained from 1D and 2D chemical shift correlation measurements . Compounds 2 and 3 are less potent antibiotics than angolamycin. Cesk Epidemiol Mikrobiol Imunol, 1992 Aug, 41(3), 174 - 7 {Immunologic cross reactivity of beta-lactam antibiotics}; Bebrova E et al.; The authors investigated the antibody response against beta-lactam antibiotics (penicillins, cephalosporins, monolactams, carbapenes) in conjugation with allergic reactions after penicillin administration . The results revealed a high percentage of positive antibody responses against penicillin and high percentage of crossed immunological reactivity between penicillin and the other investigated preparations. Endocrinology, 1992 Aug, 131(2), 903 - 10 Structure-function relationships for the effects of various aminoglycoside antibiotics on dispersed bovine parathyroid cells; Katz CL et al.; We previously showed that the polycationic aminoglycoside antibiotic neomycin mimics the effects of high extracellular calcium (Ca2+) concentrations on several aspects of parathyroid function . In the present studies we examined the actions of several additional aminoglycosides on dispersed bovine parathyroid cells to investigate the relationship between antibiotic structure and function in eliciting Ca(2+)-like effects on intracellular second messengers and PTH release . Of the antibiotics tested, those with six amino groups (neomycin-B and -C) were most potent in inhibiting dopamine-stimulated cAMP accumulation, showing IC50 values (the concentration producing a half-maximal inhibitory effect) of 7.7 x 10(-5) and 1.5 x 10(-4) M . Gentamicin-C, paromomycin, and tobramycin, which have five amino groups, were less potent, with IC50 values of 4 x 10(-4), 10(-3), and 3.3 x 10(-4) M, respectively, while gentamicin-B, kanamycin, and ribostamycin, with four amino groups, were least potent (respective IC50 values, 2.0, 2.9, and 3 x 10(-3) M) . These antibiotics showed a similar order of potency for inhibiting PTH release, with a close correlation between their IC50 values for modulating cAMP accumulation and PTH release (r = 0.98; P less than 0.001) . Finally, they showed qualitatively similar potencies for eliciting transient increases in the cytosolic free Ca2+ concentration arising from the release of Ca2+ from intracellular stores . Neomycin-B and -C both acted at 10(-4) M; gentamicin-C, paromomycin, and tobramycin evoked free intracellular Ca2+ spikes at 1.4 x 10(-4) to 6.3 x 10(-4) M; and gentamicin-B, kanamycin, and ribostamycin had little or no effect at 7 x 10(-4) M, the highest concentration tested . Thus, a variety of aminoglycoside antibiotics mimic the effects of Ca2+ and other polyvalent cations on parathyroid function . Their relative potencies are closely related to the total number of amino groups on the molecule, with a 5- to 6-fold increase in potency for each additional amino group between four and six. J Antimicrob Chemother, 1992 Aug, 30(2), 129 - 34 Inactivation of new carbapenem antibiotics by dehydropeptidase-I from porcine and human renal cortex; Hikida M et al.; The stability of the new carbapenem antibiotics, panipenem, meropenem and LJC 10,627, against porcine and human renal dehydropeptidase-I (DHP-I) was compared with that of imipenem . The order of stability to hydrolysis by renal DHP-I was: LJC 10,627 greater than meropenem greater than panipenem greater than imipenem . After incubation of the drugs with porcine or human enzyme at 30 degrees C for 4 h, the percentages of residual activity were as follows: LJC 10,627, 73.7% and 95.6%, respectively; meropenem, 0.2% and 28.7%, respectively; panipenem, 0% and 4.3%, respectively; and imipenem, 0% and 0.1%, respectively . These results demonstrate that LJC 10,627 has extremely high stability against renal DHP-I. Antibiot Khimioter, 1992 Aug, 37(8), 24 - 7 {Chemical modification of an antineoplastic antibiotic bleomycetin by the C-end fragment}; Andronnikova GP et al.; Bleomycetin, an antitumor antibiotic, was subjected to chemical modification by the C-end fragment i.e . the residue of 3-{(4-aminobutyl)amino}propylamine (spermidine++) with acylation, carbamoylation and reducing alkylation, which yielded its new semisynthetic derivatives . The use of physicochemical methods showed that the chemical modification involved the primary and secondary amino groups++ of spermidine++ and gave rise to N,N'-diacyl, N,N'-dicarbamoyl and N,N'-dialkyl bleomycetins . The biological properties of the derivatives, i.e . their cytotoxic activity, acute and pulmonary toxicities were studied . The transformation of bleomycetin by the C-end fragment lowered the antibiotic toxicity and was believed to be a promising approach to modifying its molecule. J Photochem Photobiol B, 1992 Jul 30, 14(4), 329 - 43 The extra-weak chemiluminescence generated during oxidation of some tetracycline antibiotics . 1 . Autoxidation; Kruk I et al.; Chemiluminescence (CL) appearing during autoxidation of tetracycline (TC) antibiotics has been studied . The CL spectrum consists of four emission bands with maxima at 520, 585, 640 and 700 nm . The bands at 585, 640 and 700 nm are similar to those observed for singlet molecular oxygen (1O2) . The effect of 1O2 quenchers and free radical reaction inhibitors on the light emission is also reported . The data support the concept that, during the autoxidation of TCs, cytotoxic oxygen species such as HO., O2.-, H2O2 and 1O2 are formed. Biochem Biophys Res Commun, 1992 Jul 15, 186(1), 580 - 7 Product analyses in DNA strand scission by antitumor antibiotic elsamicin A; Uesugi M et al.; Elsamicin A is an antitumor antibiotic with fascinating chemical structure and a good candidate for pharmaceutical development . Molecular mechanism of DNA backbone cleavage mediated by Fe(II)-elsamicin A has been examined . Product analysis using DNA sequencing gels and HPLC reveals the production of damaged DNA fragments bearing 3'-/5'-phosphate and 3'-phosphoglycolate termini associated with formation of free base . In addition, hydrazine-trapping experiments indicate that C-4' hydroxylated abasic sites are formed concomitant with DNA degradation by Fe(II)-elsamicin A . The results lead to the conclusion that the hydroxyl radical formed in Fe(II)-elsamicin A plus dithiothreitol system oxidizes the deoxyribose moiety via hydrogen abstraction predominantly at the C-4' carbon of the deoxyribose backbone and ultimately produces strand breakage of DNA. Biomed Chromatogr, 1992 Jul-Aug, 6(4), 196 - 7 TLC separation of certain tetracycline and amino glycopeptide antibiotics; Bhushan R et al.; The separation of tetracycline and amino glycopeptide antibiotics was achieved on silica gel thin layers . Tetracycline antibiotics were resolved on a Co+2 (1.0%) impregnated silica gel layer using ethanol:acetic acid:water (10:6:6, v/v/v) as the mobile phase . Amino glycopeptide antibiotics were separated on an untreated silica gel layer using the mobile phase n-butanol:formic acid:water (6:5:7, v/v/v) . The spots of these antibiotics were located by exposing the chromatoplate to iodine vapours. Eur J Biochem, 1992 Jul 1, 207(1), 383 - 9 Inhibition of the acidification of endosomes and lysosomes by the antibiotic concanamycin B in macrophage J774; Woo JT et al.; The antibiotic concanamycin B was found to inhibit oxidized-low-density-lipoprotein(LDL)-induced accumulation of lipid droplets in the macrophage J774 at a concentration of 5-10 nM . Concanamycin B inhibited cholesteryl-ester synthesis from {14C}oleate by 50% at 14 nM without affecting the synthesis of triacylglycerol and polar lipids . Degradation of internalized oxidized 125I-LDL was inhibited by about 80% in cells treated with 25 nM concanamycin B, while cell-surface binding of oxidized 125I-LDL at 4 degrees C, uptake of surface-bound oxidized 125I-LDL and microsomal acyl-CoA:cholesterol acyltransferase activity were not significantly affected by the antibiotic at 25 nM . When J774 cells were treated with 25 nM concanamycin B at 37 degrees C for 60 min, there was a reduction of about 50% in the activity of cell-surface receptors . This reduction appeared to be due to partial trapping of the receptors within the cells . Concanamycin B significantly inhibited ATP-dependent acidification of endosomes and lysosomes of the J774 cells at a concentration of 4 nM . Since acidic condition of these organelles is required for receptor recycling and hydrolysis of lipoproteins, the results demonstrate that concanamycin-B inhibition of oxidized-LDL-induced accumulation of lipid droplets and cholesteryl esters in macrophages J774 is associated with reduced ATP-dependent acidification of these organelles. Eur J Biochem, 1992 Jul 1, 207(1), 125 - 34 Fluorescence study of the macrolide pentaene antibiotic filipin in aqueous solution and in a model system of membranes; Castanho MA et al.; The polyene antibiotic filipin (a pentaene) has been studied using photophysical techniques . The polyene self-aggregates in water with a critical micellar concentration of 2 microM . Two approaches were used to evaluate the aggregate dimensions: (a) a lower limit of 10 nm for the aggregate radius was obtained from energy transfer experiments; (b) a formula for rationalizing the turbidity spectrum was derived, and from its application a spherical shape of radius about 50 nm was deduced . The low value for the fluorescence anisotropy of the aggregate (r = 0.02) is compatible with a very loose structure, i.e . the chromophore has very efficient depolarization dynamics that is not controlled by the aggregate size . The Stern-Volmer plot of aggregated filipin fluorescence quenching by iodide is non-linear, presenting a downward curvature . A model was used for the interpretation of these data, along with a study of the quenching in transient state; it was concluded that all the components of the decay are affected by the quencher, i.e . the aggregate has a very open structure with respect to the iodide ion . The partition constants of the polyene, Kp, between a model system of membranes (small unilamellar vesicles of dipalmitoylglycerophosphocholine) and the aqueous phase were determined from anisotropy measurements; the values obtained were Kp (gel phase) = (3.4 +/- 0.8) x 10(3) and Kp (liquid crystal phase) = (7.7 +/- 2.2) x 10(2) . The observation that the polyene incorporation is efficient is at variance with the belief that the presence of sterols are essential for the interaction of polyene antibiotics with membranes {for review see Bolard, J . (1986) Biochim . Biophys . Acta 864, 257-304}. J Pediatr, 1992 Jul, 121(1), 28 - 33 Hematologic predictors of bone marrow recovery in neutropenic patients hospitalized for fever: implications for discontinuation of antibiotics and early discharge from the hospital; Griffin TC et al.; We evaluated the timing and pattern of changes in the complete blood cell count that preceded marrow recovery during 107 consecutive episodes of fever and neutropenia in 64 children with cancer . Four measures derived from serial daily measurement of the complete blood cell count were evaluated: total leukocyte count, absolute neutrophil count, absolute phagocyte count, and platelet count . During 70 (65%) of these 107 episodes, patients were discharged with an absolute neutrophil count of fewer than 500 cells/mm3; 24 patients were discharged from the hospital despite an absolute neutrophil count of fewer than 100 cells/mm3 . During all but one of these 70 episodes, however, signs of early marrow recovery were present before discharge; sustained increases were observed in these patients' leukocyte, absolute neutrophil, absolute phagocyte, and platelet counts 2 or more days before their discharge in 41%, 49%, 50%, and 39% of cases, respectively . Although they were neutropenic at discharge, most patients had signs of multilineage marrow recovery at that time; 59 of 70 had increases in three of four of the measurements that we studied . None of the 69 patients who had evidence of marrow recovery at discharge had recurrence of fever . We conclude that children with cancer who were hospitalized for fever during periods of neutropenia have increases in the peripheral blood cell count that herald imminent bone marrow recovery, often several days before the absolute neutrophil count recovers to 500 cells/mm3 . Our success in discharging such patients before resolution of neutropenia suggests that further controlled trials are needed to evaluate the safety and feasibility of cessation of antibiotic therapy and early discharge from the hospital. J Bacteriol, 1992 Jul, 174(13), 4331 - 7 Increase of sensitivity to aminoglycoside antibiotics by polyamine-induced protein (oligopeptide-binding protein) in Escherichia coli; Kashiwagi K et al.; The sensitivity of Escherichia coli to several aminoglycoside antibiotics was examined with E . coli DR112 transformed by the gene for polyamine-induced protein (oligopeptide-binding {OppA} protein) or polyamine transport proteins . The results clearly showed that sensitivity to aminoglycoside antibiotics (gentamicin, isepamicin, kanamycin, neomycin, paromomycin, and streptomycin) increased due to the highly expressed OppA protein . When the gene for OppA protein was deleted, sensitivity to aminoglycoside antibiotics was greatly decreased . It was also shown that isepamicin could bind to OppA protein with a binding affinity constant of 8.5 x 10(3) M-1 under the ionic conditions of 50 mM K+ and 1 mM Mg2+ at pH 7.5, and isepamicin uptake into cells was greatly stimulated by the OppA protein . These results, taken together, show that the OppA protein increases the uptake of aminoglycoside antibiotics . In addition, the OppA protein increased the transport of spermidine and an oligopeptide (Gly-Leu-Tyr) . The uptake of isepamicin into cells was partially inhibited by spermidine, suggesting that the binding site for isepamicin overlaps that for spermidine on the OppA protein . Spermidine uptake activity by the OppA protein was less than 1% of that of the ordinary spermidine uptake system . Aminoglycoside antibiotics neither stimulated the synthesis of OppA protein nor increased spermidine uptake. J Am Acad Dermatol, 1992 Jul, 27(1), 34 - 7 Failure of Borrelia burgdorferi to survive in the skin of patients with antibiotic-treated Lyme disease; Berger BW et al.; BACKGROUND: Borrelia burgdorferi has been cultivated from clinically normal skin (previous erythema migrans sites) after antibiotic therapy for Lyme disease . OBJECTIVE: We investigated the possibility of similar findings in 13 of our patients with antibiotic-treated Lyme disease from whom B . burgdorferi was cultivated from their erythema migrans lesions before antibiotic therapy . METHODS: After treatment with doxycycline or a combination of amoxicillin and probenecid, skin biopsy specimens were obtained from clinically normal skin adjacent to the previous biopsy sites and cultured . RESULTS: B . burgdorferi was not cultivated from these posttreatment biopsy sites . CONCLUSION: The failure of B . burgdorferi to survive in the former erythema migrans sites of our antibiotic-treated patients, as well as their favorable clinical response, supports the use of doxycycline or combined amoxicillin and probenecid in the treatment of early Lyme disease but does not preclude the survival of the organism in other tissues. Obstet Gynecol, 1992 Jul, 80(1), 117 - 22 Predictors of antibiotic prophylactic failure in post-cesarean endometritis; Chang PL et al.; Despite the use of prophylactic antibiotics, endometritis occurs in 1-31% of patients after cesarean delivery . We sought to identify predictors of prophylactic antibiotic failure . In a retrospective review of 1800 cesarean deliveries, 766 patients had either ampicillin or cefazolin prophylaxis; 240 (31.3%) developed endometritis . Stepwise logistic regression identified the number of vaginal examinations (P less than .001), nulliparity (P = .001), low gestational age (P = .033), and cefazolin use (P = .002) as predictors of endometritis . One in two women with six or more vaginal examinations before cesarean delivery will have prophylactic failure . In preterm gestations (N = 177), the number of vaginal examinations was the single predictor of prophylactic antibiotic failure (P = .002) . The number of vaginal examinations can be used to design new strategies to prevent a high rate of prophylactic failure. J Laryngol Otol, 1992 Jul, 106(7), 621 - 4 Role of prophylactic antibiotics in surgery for advanced head and neck cancer; Tandon DA et al.; Four regimens of prophylactic antibiotics were utilized in 122 consecutive patients of stages III and IV carcinoma of the upper aero-digestive tract undergoing major resections in a randomized single-blind study . Ampicillin, gentamicin, cephalexin and metronidazole were used in different combinations for periods of 5 or 10 days . A cephalexin-metronidazole protocol for 10 days was associated with lowest post-operative infection rate . Oral-oropharyngeal resection and use of pectoralis major myocutaneous flap were the most important factors contributing to infection. J Antibiot (Tokyo), 1992 Jul, 45(7), 1133 - 8 Studies on viridenomycin, a novel 24-membered macrocyclic polyene lactam antibiotic; Nakagawa M et al.; A new antitumor antibiotic, designated AL081, was obtained from the culture filtrate of an actinomycete identified as Streptomyces gannmycicus, and found to be identical with viridenomycin by direct comparison . The structure of the antibiotic was determined by NMR spectral analysis including a variety of two-dimensional techniques to be a novel 24-membered macrocyclic polyene lactam . Viridenomycin prolonged the survival periods of mice bearing P388 leukemia and B16 melanoma cells. J Anal Toxicol, 1992 Jul-Aug, 16(4), 223 - 7 Mass spectral characterization of three anthracycline antibiotics: a comparison of thermospray mass spectrometry to particle beam mass spectrometry; Bloom J et al.; Mass spectral results for three anthracyclines, doxorubicin, daunorubicin, and carminomycin are compared by using thermospray (TS) or particle beam (PB) {electron ionization (EI) and chemical ionization (CI)} instruments . Typically, positive ion TS mass spectrometry (MS) provided intense {MH}+ ions and some fragment ions, while PBMS in the EI mode provided only fragment ions . Significant {MH}+ ions were observed for carminomycin and daunorubicin when analyzed using PBMS in the positive ion CI mode . Under negative ion detection, TSMS yielded intense {M-H}- ions for these compounds while PBCIMS resulted in significant M- ions . Fragment ions observed in all three anthracyclines under positive and negative ion detection by TSMS and PBCIMS are due mainly to the cleavage of glycosidic bond, loss of H2O, and the loss of the side chain (COCH2R2) from the aglycone. Antibiot Khimioter, 1992 Jul, 37(7), 43 - 4 {Antibiotic therapy of children in a gnotobiological unit}; Koliadenko VF et al.; The clinical effect of antibiotics in treatment of children at the age of 2 months to 5 years with acute pneumonia during a gnotobiological department in the wards of the 1st class purity and under the conditions of a routine pediatric hospital was estimated . The course of the antibiotic therapy amounted to 4.7 +/- 0.42 days in the gnotobiological department and 12.0 +/- 0.3 days in the routine hospital . After recovery the patients were discharged in 7.61 +/- 0.76 days from the gnotobiological department and in 15.2 +/- 1.11 days from the routine hospital. Vet Surg, 1992 Jul-Aug, 21(4), 286 - 92 Regional limb perfusion with antibiotics in three horses; Whitehair KJ et al.; Antibiotics were delivered to chronically infected tissues by regional limb perfusion in three horses with osteomyelitis associated with orthopedic implants . Two infections were resolved with implants in place; in one, a sequestrum was resorbed . In one horse, regional antibiotic perfusion was applied to treat progressively worsening bone infection after initial implants loosened and were removed. Vet Surg, 1992 Jul-Aug, 21(4), 279 - 85 Regional perfusion of the equine carpus for antibiotic delivery; Whitehair KJ et al.; Regional perfusion of carpal tissues by forced intramedullary administration of fluids was evaluated in 10 horses . Results of subtraction radiography after perfusion with a contrast medium demonstrated that perfusate was delivered to the carpal tissues by the venous system . Perfused India ink was distributed uniformly in the antebrachiocarpal and middle carpal synovial membranes . Histologically, the ink was within the venules of the synovial villi . Immediately after perfusion with gentamicin sulfate (1 g), the gentamicin concentrations in the synovial fluid and synovial membrane of the antebrachiocarpal joint were 349 +/- 240 micrograms/mL and 358 +/- 264 micrograms/g, respectively . When gentamicin concentrations in the synovial fluid of the antebrachiocarpal joint and serum were measured 0, 0.5, 1, 4, 8, 12, and 24 hours after carpal perfusion, the mean peak gentamicin concentration in the synovial fluid was 589 +/- 429 micrograms/mL . At hour 24, the mean gentamicin concentration in the synovial fluid was 4.8 +/- 2.0 micrograms/mL . The resulting peak gentamicin concentration in the serum was 23.7 +/- 14.5 micrograms/mL immediately after the perfusion; it decreased below the desired trough level of 1 micrograms/mL between hours 4 and 8. Cesk Farm, 1992 Jul, 41(4-5), 162 - 5 {Antibiotic consumption in relation to sex and age}; Luknarova N et al.; The present paper aims at an analysis of the consumption of antibiotics in relation to age, sex and diagnosis in the district of Bratislava-vidiek . The prescription of 17 primary out-patient care physicians was evaluated . The set under study included 17,771 inhabitants divided into 10 age categories . Drug consumption was expressed by the number of packages per 1000 inhabitants and a month . The processed data were statistically evaluated . The results of the paper showed a higher consumption in women . Within the framework of the age categories under study, the consumption of antibiotics does not increase with age . The highest consumption of antibiotics, 70.45%, was found in the diseases of the respiratory system, the consumption in acute diseases being 60.46% . Tetracycline and penicillin antibiotics are the most frequently used preparations in the population under study. J Burn Care Rehabil, 1992 Jul-Aug, 13(4), 407 - 9 Antibiotic iontophoresis in the management of burned ears; Rigano W et al.; Severe deformities of the ears are a distressing problem after burn injury . Successful management of chondritis has been elusive . Antibiotic iontophoresis has been used in the management of burned ears in patients who have been admitted to the St . Vincent Medical Center Burn Unit since 1983 . There were 145 ear burns in 92 consecutive patients who received prophylactic penicillin or gentamicin iontophoresis and who were admitted from 1983 through 1990 . A retrospective analysis of all patients who were admitted to the burn unit from 1967 to 1983 was done to review the outcome for patients with burned ears when conventional treatment was used . The incidence of infection, need for chondrectomy, and ear infection were virtually eliminated by management with antibiotic iontophoresis . In addition, no complications were noted when antibiotic iontophoresis was used . Antibiotic iontophoresis provides a safe, simple, and effective way to manage burned ears and thereby limits postburn ear deformities. J Pharm Sci, 1992 Jul, 81(7), 663 - 6 Determination of a cephalosporin antibiotic, ceftibuten, in human plasma with column-switching high-performance liquid chromatography with ultraviolet detection; Pan HT et al.; A column-switching high-performance liquid chromatographic assay combined with a heart-cutting technique and UV detection (LC/LC/UV) was developed to determine ceftibuten, a new oral cephalosporin, in human plasma . Plasma samples were directly injected into the first chromatographic column for sample cleanup and extraction . Thereafter, a switching valve, located at the junction of the first cleanup column and the second analytical column, opened during a 4-6-min interval after injection to transfer the segment containing ceftibuten into the analytical column for quantitation . The method was used routinely in pharmacokinetic studies and has the advantages of simplicity, improved sensitivity, and selectivity . Concentrations of ceftibuten in plasma over a range of 0.1-20 micrograms/mL can be determined with high precision and reproducibility . A single, oral, 200-mg dose of ceftibuten in humans resulted in a maximum concentration of 9.79 micrograms/mL, an area under the plot of concentration of drug in plasma versus time (0-12 h) of 47.77 micrograms.h/mL, and a half-life of 3.2 h . These results document the utility of the LC/LC/UV method in clinical pharmacokinetic studies. Int J Clin Pharmacol Ther Toxicol, 1992 Jul, 30(7), 257 - 9 Cutaneous adverse reactions following the administration of nonsteroidal antiinflammatory drugs and antibiotics: an Italian survey; Bottoni A et al.; The Italian Group for Epidemiological Research in Dermatology (GISED) collected a series of cutaneous adverse reactions following NSAID and/or antibiotics administered by topical and/or systemic route . Dermatologists from North and Central Italy took part in this survey by filling in 1457 case report forms during a four-month observation time in 1988-89 . The main purpose of our epidemiological study aimed at evaluating a post-marketing surveillance program by examining spontaneous reports of cutaneous adverse reactions . This result seems to be noteworthy, considering the difficulties encountered in Italy to develop such a program. Biosci Biotechnol Biochem, 1992 Jul, 56(7), 1079 - 85 Structural elucidation of minor components of peptidyl antibiotic P168s (leucinostatins) by tandem mass spectrometry; Isogai A et al.; Tandem mass spectrometry with a four-sector type mass spectrometer was used to elucidate the structures of minor components of the peptidyl antibiotic P168s (leucinostatins) . As N-terminal fragments, ions by B-type cleavage were dominant, while V-type cleavages were observed along with X, Y, and Z types as C-terminal ions . The V-type ions were predominant in the cleavages of the amino terminals of leucyl and hydroxyleucyl residues . The structures of several minor components could be deduced from the tandem mass spectra. Schweiz Rundsch Med Prax, 1992 Jun 30, 81(27-28), 875 - 8 {Antibiotic therapy in ambulatory surgery}; Picard G et al.; Antibiotic therapy in outpatient surgical care is reviewed . In the first section some skin and soft-tissue infections are discussed, where antibiotics are likely to achieve clinical cure . In the second section we examine, where surgical treatment alone is essential for successful eradication of the infection . Wound management, where antibiotics are still controversial, is mentioned in the last section . Some pharmacological data on the discussed antibiotics are given. Chem Biol Interact, 1992 Jun 15, 83(1), 23 - 33 Interaction between antitumor antibiotic chromomycin A3 and Mg2+ . I . Evidence for the formation of two types of chromomycin A3-Mg2+ complexes; Aich P et al.; Chromomycin A3 (CHRA3) is an antitumor antibiotic which binds to Mg2+ . In the present communication, we show, by means of equilibrium spectroscopic studies (such as absorption, fluorescence and circular dichroism), that two types of CHRA3-Mg2+ complexes (of 1:1 and 1.9:1 stoichiometries in terms of CHRA3:Mg2+, respectively) are formed depending on the concentrations of CHRA3 and Mg2+ . The rate constant and activation energy for the formation of two complexes are different, thereby reinforcing the proposition that they are different molecular species . This observation is novel and significant in order to understand the anticancer property of the drug . It also provides explanation for earlier observations that site, affinity parameters and mode of interaction of the drug with DNA in the presence of Mg2+ depend on the relative concentration of Mg2+. Gene, 1992 Jun 15, 115(1-2), 55 - 60 Identification of Streptomyces coelicolor genes involved in regulation of antibiotic synthesis; Champness W et al.; To define genetic elements that regulate antibiotic synthesis, we screened for mutations that visibly blocked synthesis of Streptomyces coelicolor's two pigmented antibiotics and found mutant strains in which all four antibiotics were blocked . The responsible mutations defined two loci, absA and absB . Two additional approaches to defining genes have been taken: isolation of cloned genes with a dominant negative effect on antibiotic synthesis and isolation of genes which, in multicopy, can compensate for specific mutational blocks . These genes apparently function in a global regulatory pathway (or network) for control of antibiotic synthesis. Br J Surg, 1992 Jun, 79(6), 525 - 8 Effect of antibiotics in fibrin sealant on healing colonic anastomoses in the rat; van der Ham AC et al.; In 90 rats a colonic anastomosis was constructed with 12 interrupted 7/0 polypropylene sutures . Group 1 (n = 30) served as a control group . In group 2 (n = 30) the anastomosis was sealed with fibrin adhesive and in group 3 (n = 30) a mixture of fibrin, clindamycin and cefotaxime was used . On days 2, 4 and 7, ten animals in each group were killed . Adhesion formation was significantly increased in groups 2 and 3 compared with the control group . On day 2 the anastomosis was significantly stronger after sealing with antibiotic-fibrin mixture . On day 4 the bursting pressure in group 2 was significantly lower than in groups 1 and 3 . At the same time the concentration of hydroxyproline was significantly reduced in group 2, but not in group 3 . The addition of antibiotics prevents the negative effect of fibrin adhesive on the healing colonic anastomosis and contributes to a stronger anastomosis on day 2 after operation. Arch Surg, 1992 Jun, 127(6), 745 - 6 Implantation of antibiotic-releasing carriers and in situ reconstruction for treatment of mycotic aneurysm; Pasic M et al.; Four patients with mycotic aneurysm of the extracranial carotid artery, the innominate artery, the ascending aorta, and the infrarenal aorta were treated with local implantation of antibiotic-releasing carriers after resection of the aneurysm, excision of all infected tissue, and in situ reconstruction by prosthetic graft replacement in two patients and patch plasty in two patients . The patient with a mycotic aneurysm of the ascending aorta was operated on again 1 month after the first operation because of a second mycotic aneurysm located on the aortic arch . No early or late signs of recurrent infection were seen on clinical and laboratory postoperative follow-up done between 9 and 16 months or on duplex scan or computed tomography done at these times . Implantation of antibiotic-releasing carriers after debridement of all infected tissue and in situ reconstruction for treatment of mycotic aneurysm was performed successfully in four patients with this life-threatening condition. Cesk Farm, 1992 Jun, 41(3), 105 - 7 {Detection of antibiotics in biological materials for purposes of toxicologic analysis . II . Detection of tetracyclines in biological materials}; Novakova E; A method of demonstration of tetracycline antibiotics elaborated as a model was used in toxicological practice . Urines of patients were analyzed after therapeutic doses and after large doses taken with suicidal intentions . At the same time, also excretion of these antibiotics from the organism was investigated . All antibiotics under study were found in the original form; in tetracycline other substances, identified as 4-epitetracycline and 4-epianhydrotetracycline, regularly appeared . A question is discussed whether these substances can be considered to be real metabolites or only products of epimerization . The importance of 4-epianhydrotetracycline for analytical purpose and interpretation of the finding is pointed out. J Nat Prod, 1992 Jun, 55(6), 753 - 9 Isolation and structure determination of new macrolide antibiotics; Hatfield GM et al.; Three new bafilomycin-like compounds PD 118,576-A1 {1}, PD 118,576-A2 {2}, and PD 118,576-A3 {3} were isolated from a new soil Streptomyces species (WP 3913) . The structures of PD 118,576-A1, PD 118,576-A2, and PD 118,576-A3 were elucidated on the basis of spectroscopic studies including 2D nmr. Indian J Med Res, 1992 Jun, 96, 186 - 91 Antibiotics & glycosaminoglycan metabolism in rats; Amma KS et al.; The administration of antibiotics to rats resulted in significant alteration in the metabolism of glycosaminoglycans (GAG) . The concentrations of the total GAG and most of the fractions increased in the aorta and liver in rats given tetracycline and cephalosporin, but decreased in ampicillin and streptomycin treated groups . The activity of biosynthetic enzymes of GAG in the liver increased significantly with all the antibiotics administered, except streptomycin . The pattern of change in the activity of many of the degrading enzymes of GAG in the liver and aorta was not uniform in different antibiotics administered groups . The changes observed in the activities of biosynthetic and degrading enzymes of GAG in the liver and aorta in different antibiotics administered groups may account for the alterations in the level of GAG observed in different experimental groups. Dtsch Tierarztl Wochenschr, 1992 Jun, 99(6), 249 - 54 {Evaluation of fixed glucocorticoid-antibiotic combinations}; Ungemach FR; Fixed combinations of glucocorticoids and antibiotics are widely used for the treatment of bacterial infections because they can cause a rapid relief of the inflammatory symptoms . However, hitherto a decisive improvement of the clinical efficacy of the combination as compared to single antibiotic therapy could not be proved . Without a real clinical advantage the combined use of glucocorticoids causes severe side effects like immune suppression with increased risk of infections, gastrointestinal lesions and depression of endogenous hydrocortisone which all will occur even after short-term use and may last for several weeks . Glucocorticoids exhibit a markedly longer duration of action than antibiotics with the risk of cumulation of the glucocorticoid . Thus, there is no kinetic compatibility as it has to be claimed for a rational combination . Due to the negative risk-benefit relation the systemic use of such combinations has to be rejected . For the topical treatment of skin disorders, however, the short-term use of combinations of corticosteroids and antibiotics with comparable pharmacokinetics on the skin like aminoglycoside antibiotics can be of clinical benefit. J Antibiot (Tokyo), 1992 Jun, 45(6), 875 - 8 A new antitumor antibiotic product, demethylchartreusin . Isolation and biological activities; Aoyama Y et al.; A new antitumor antibiotic, 3''-demethylchartreusin was isolated from the culture broth of Streptomyces chartreusis, as a minor component of crude chartreusin . It is structurally related to chartreusin, containing same aglycone of chartreusin, but different sugar moieties . 3''-Demethylchartreusin exhibits some potent inhibitory activities against murine tumors. J Antibiot (Tokyo), 1992 Jun, 45(6), 824 - 31 Structures of new peptide antibiotics, plusbacins A1-A4 and B1-B4; Shoji J et al.; The constituent amino acids of plusbacins A1-A4 were determined to be two moles of L-trans-3-hydroxyproline and one mole each of D-threo-beta-hydroxyaspartic acid, L-threo-beta-hydroxyaspartic acid, D-allo-threonine, D-serine, D-alanine and L-arginine . In plusbacins B1-B4, one mole of L-trans-3-hydroxyproline is replaced by L-proline . The fatty acid residue of A1 and B1 was determined to be 3-hydroxy-tetradecanoic acid, for A2 and B2 to be 3-hydroxy-isopentadecanoic acid, for A3 and B3 to be 3-hydroxy-isohexadecanoic acid, and for A4 and B4 to be 3-hydroxy-hexadecanoic acid . A lactone linkage was suggested to reside between L-threo-beta-hydroxyaspartic acid and 3-hydroxy-fatty acid residues by degradation experiments . The amino acid sequences of plusbacins A2 and B2 were confirmed by Edman degradation of their deacylated products, and supported by mass spectrometric studies . From the above, structures of all components of plusbacins were concluded. Biull Eksp Biol Med, 1992 Jun, 113(6), 636 - 8 {Quantitative determination of anthracycline antibiotic binding with DNA}; Bogush TA et al.; A new method of quantitative intravital assessment of anthracyclines accumulation and binding with DNA in alive cells has been developed . For this purpose DNA specific fluorescent dye Hoechst 33258 was used . Extent of fluorescence quenching of bound with DNA dye correlated with binding of daunomycin with cell DNA after mixing solutions of the drug and cells . It allowed us to determine quantity of drug molecules bound with DNA in the cells during the time. Tuber Lung Dis, 1992 Jun, 73(3), 134 - 6 In vitro activity of meropenem and imipenem against mycobacteria: development of a daily antibiotic dosing schedule; Watt B et al.; The activity of two carbapenem antibiotics, meropenem and imipenem, against Mycobacterium species was assessed by means of the Bactec 460 radiometric apparatus . This system allowed a result to be read in 4-10 days . The instability of imipenem, particularly, in the test system necessitated the development of a regimen of daily addition of antibiotic to permit a more accurate assessment of antibiotic activity to be made . When antibiotic-containing media are incubated for long periods, as is the case when determining antimycobacterial activity, the stability of test antibiotics is an important factor that must be considered. Antibiot Khimioter, 1992 Jun, 37(6), 24 - 6 {Effect of indirect endolymphatic antibiotic therapy on clinical and immunological indicators in patients with erysipelas of the lower extremities}; Levina LD et al.; Two groups of patients with erysipelas of the lower extremities underwent indirect endolymphatic therapy with bicillin-3 (58 patients) and routine penicillin therapy (79 patients) . Comparative clinicoimmunological examinations in the two groups revealed that lymphotropic administration of the antibiotic had a more favourable effect on the disease process, as evidenced by more rapid reverse time courses of erysipelas clinical signs, less frequent incidence of early relapses and normalization of the majority of immunological parameters by the end of the treatment . For estimation of the anti-recurrence efficacy of the antibiotic therapy in the patients with erysipelas, it was recommended to use a specific scale based on the principles of the Wald successive alternative analysis. J S C Med Assoc, 1992 Jun, 88(6), 291 - 5 Postcesarean endometritis: a brief review and comparison of three antibiotic regimens; Filler L et al.; Three different antibiotic regimens (trospectomycin plus azteonam, clindamycin plus azteonam, and triple antibiotics-ampicillin plus clindamycin plus gentamicin) were all effective in treating patients with postcesarean endometritis . Patients are frequently cured clinically despite the fact that the offending organisms may be isolated in post-treatment cultures . Treatment of postcesarean endometritis without obtaining endometrial cultures is acceptable gynecologic practice . Obtaining post-treatment cultures is clearly not cost effective nor clinically beneficial . Drug treatment efficacy should be evaluated by clinical response . This communication is the first to report the new antibiotic, trospectomycin, in the treatment of postcesarean endometritis . Further clinical trials are currently underway. J Pharm Sci, 1992 Jun, 81(6), 529 - 31 Self-setting hydroxyapatite cement: a novel skeletal drug-delivery system for antibiotics; Yu D et al.; A novel approach using a self-setting hydroxyapatite (HAP) cement as a skeletal drug-delivery system has been proposed to solve the problem of delivering drugs to skeletal tissue at sufficiently high local concentrations for desirable therapeutic effects . HAP cements loaded with antibiotics can be formed in situ and can be used as bonding materials between bone and prostheses, as well as drug-release devices . The cement also possesses sufficient mechanical strength to be a potential bone grafting material . Using cephalexin and norfloxacin as model drugs, we observed continuous in vitro release profiles of these compounds from cement pellets loaded 0.9-4.8% by weight with one of the drugs . This drug-release pattern correlated well with the Higuchi model . This hydroxyapatite cement drug-delivery system can be applied in the treatment of osteomyelitis and infected compound fractures. Brain Res, 1992 May 15, 580(1-2), 345 - 7 Effects of Ca2+ antagonists and aminoglycoside antibiotics on Ca2+ current in isolated outer hair cells of guinea pig cochlea; Nakagawa T et al.; The effects of various Ca2+ antagonists and aminoglycoside antibiotics on the Ca2+ channel in isolated outer hair cells of the guinea pig were investigated using a whole-cell patch-clamp technique . The inhibitory action was in the order of La3+ much greater than Cd2+ much greater than Ni2+ greater than Co2+ for inorganic Ca2+ antagonists, and flunarizine = nicardipine greater than omega-conotoxin greater than methoxyverapamil = diltiazem much greater than amiloride for organic ones . Aminoglycoside antibiotics also had antagonistic effects on the Ca2+ channel. Helv Chir Acta, 1992 May, 58(6), 775 - 8 {Dangerous hypoprothrombinemic hemorrhage in antibiotic therapy}; Stieger R et al.; Antibiotics can be associated with hypoprothrombinaemic haemorrhages in risk patients . Risk factors are: poor nutrition, impaired liver- or renal function, coagulation depleting medical therapy or illness . Pathogenetically there is a vitamin K deficiency with reduction of vitamin K dependent clotting factors; mainly by decreased vitamin K synthesis in intestinal bacterias . In consequence every risk patient under antibiotics should receive vitamin K prophylactically and in a parenteral way, because of unreliable resorption in gastrointestinal tract . Prothrombin-time-monitoring is essential to recognize the hypoprothrombinemia in every risk patient under antibiotics. J Antibiot (Tokyo), 1992 May, 45(5), 618 - 23 Deoxymulundocandin--a new echinocandin type antifungal antibiotic; Mukhopadhyay T et al.; A new echinocandin type antifungal antibiotic, deoxymulundocandin, C48H77N7O15, was isolated from the culture filtrate and mycelia of a fungal culture, Aspergillus sydowii (Bainier and Sartory) Thom and Church var . nov . mulundensis Roy (Culture No . Y-30462) . The structure was established by comparative GC-MS analyses of the derivatized acid hydrolysates of deoxymulundocandin and mulundocandin as well as by the high field NMR experiments (COSY, NOESY and DEPT). J Antibiot (Tokyo), 1992 May, 45(5), 607 - 12 Sporeamicin A, a new macrolide antibiotic . II . Structure determination; Morishita A et al.; Structure of a novel antibiotic, sporeamicin A (SRM-A), was determined by a combination of spectroscopic and X-ray crystallographic studies . SRM-A has a unique structure containing a 2,3-dihydro-3-oxofuran moiety as part of a 14-membered macrolide ring. Am Surg, 1992 May, 58(5), 280 - 3 Selective versus routine antibiotic use in acute appendicitis; Nguyen BL et al.; Whether prophylactic antibiotics should be employed routinely in all patients with presumed appendicitis rather than be administered selectively to those with suspected perforation remains a controversial issue . The outcome of 312 adult patients undergoing appendectomy during periods of selective (I, n = 153) and routine (II, n = 159) antibiotic use were compared . Although the rates of misdiagnosis were comparable (9% vs 13%), significantly more patients with appendicitis in Period II had perforated appendicitis (29 of 139 vs 44 of 139, P less than 0.05) . Prophylactic antibiotics were given to 43 (28%) patients in Period I compared to 132 (83%) in Period II (P less than 0.001) . This, increased frequency was true for both simple (21% vs 81%, P less than 0.001) and perforated (66% vs 86%, P less than 0.05) appendicitis . A single antibiotic, most frequently a cephalosporin, was used significantly more often in Period II (44% vs 82%, P less than 0.001) . There was no significant difference in the methods of wound closure between the two periods . The incidence of infectious complications was similar in patients with simple appendicitis in both periods (8% vs 11%), but it was significantly greater during Period I in patients with perforated appendicitis (45% vs 20%, P less than 0.05) . The overall infection rate was similar in both periods (16% vs 22%) . Thus, high-risk patients with perforated appendicitis were more likely to receive antibiotics and had a lower infection rate with routine antibiotic use . Furthermore, there was no overall change in the infection rate during this period, despite the use of less toxic, single drug regimens and a greater percentage of perforated appendicitis. J Chromatogr, 1992 May 1, 598(1), 23 - 31 Evaluation of restricted access media for high-performance liquid chromatographic analysis of sulfonamide antibiotic residues in bovine serum; Brewster JD et al.; Three commercially-available high-performance liquid chromatographic columns packed with restricted access media were evaluated for suitability in multi-residue direct injection analysis at the ng/ml level . The internal surface reversed-phase and shielded hydrophobic phase columns were not sufficiently retentive to separate all analytes from the tail of the matrix peak . Coelution of some of the analytes was also observed with these columns . The semi-permeable surface column was significantly more retentive and selective, providing good separation of analyte and matrix peaks . With this column, an analytical protocol requiring no organic solvents was developed for the assay of six sulfonamides at a detection limit of 25 ng/ml. Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4 Suppl), 85S - 89S Comparison of two oral antibiotics, roxithromycin and amoxicillin plus clavulanic acid, in lower respiratory tract infections; Dautzenberg B et al.; In a randomized, multicenter, open-label study, 490 ambulatory adult patients with lower respiratory tract infection (LRTI) were randomized to roxithromycin (ROX) 150 mg b.i.d . orally (n = 244) or amoxicillin plus clavulanic acid (AMX + CA) as 500 mg AMX + 125 mg CA t.i.d orally (n = 24) . Clinical results were analyzed in 477 patients with acute bronchitis (79%), chronic bronchitis (CB) (14%), and pneumonia (7%) . There were significantly more patients with underlying disease (cardiovascular diseases, p = 0.045; and alcoholism, (p less than 0.001), and more patients over the age of 65 years (p = 0.045) in the ROX group . Overall clinical efficacy was similar in both groups: 88% (206:235) in the ROX group and 85% (205:242) in the AMX + CA group . Side effects were reported in 67 cases (28%) in the AMX + CA group and in 21 cases (9%) in the ROX group (p less than 0.0001), causing withdrawal in 21 and three cases, respectively (p less than 0.001) . Thus, despite being administered to a significantly older and more ill group of patients with LRTI, roxithromycin was as effective as amoxicillin plus clavulanic acid and better tolerated. Diagn Microbiol Infect Dis, 1992 May-Jun, 15(4 Suppl), 103S - 109S Factors affecting nonadherence with antibiotics; Sanson-Fisher R et al.; Nonadherence with antibiotic therapy has profound implications both for patient health and the health care system that bears the financial costs incurred . Significant levels of nonadherence with antibiotic prescriptions have been demonstrated . Of the many proposed variables involved, those that are potentially modifiable relate to aspects of the doctor-patient interaction and drug regimen . Despite the potential for intervention with these variables, there have been very few methodologically sound studies examining their effect on adherence with either medications generally or antibiotics specifically . Only two studies were located that had tested the effectiveness of reduced complexity of antibiotic dosage schedules . The results suggest that the less complex the schedule, the greater is the adherence . Both practitioners and patients must be encouraged to use and accept simpler dosage schedules, preferably once-daily schedules wherever possible . The paucity of well-controlled studies to date highlights the need for further research evaluating intervention strategies that utilize variations in dosage schedule and elements of the doctor-patient interaction to improve adherence with antibiotic medications. Mo Med, 1992 May, 89(5), 289 - 93 The role of antibiotics in the management of acute exacerbation of chronic bronchitis (answers to some commonly asked questions); Skudlarska BA et al.; More than 7 million Americans suffer from chronic bronchitis, and it has been estimated that each of these patients will experience between one and four acute exacerbations a year . This problem constitutes a major social and financial burden on our society . Despite the prevalence of this disorder there is still considerable disagreement among physicians as to appropriate treatment, especially with regard to the use of antibiotics . Though the role of antibiotics is unclear, the pharmaceutical industry is trying to obtain regulatory approval of several new antibiotics for use in exacerbations of chronic bronchitis . We examine the role of antibiotics in the management of chronic bronchitis. Am Fam Physician, 1992 May, 45(5), 2237 - 41 Antibiotic-associated neutropenia; Walbroehl GS et al.; Neutropenia is an uncommon but potentially serious complication of drug therapy . Many drugs, especially antibiotics, can produce this untoward effect . Typically, drug-induced neutropenia occurs in a patient receiving a semisynthetic penicillin for two weeks or more . The cause is believed to be either a hypersensitivity reaction or a toxic dose-related suppression of white blood cell precursors . Most patients improve after discontinuation of the drug. Arch Otolaryngol Head Neck Surg, 1992 May, 118(5), 488 - 90 Prophylactic antibiotics for head and neck surgery with flap reconstruction; Johnson JT et al.; The leading cause of postoperative morbidity in patients undergoing major head and neck surgical procedures is postoperative infection . This prospective randomized multi-institutional clinical trial was designed to compare the effectiveness of clindamycin phosphate and high-dose cefazolin sodium therapy in preventing postoperative wound sepsis in patients undergoing contaminated head and neck surgical procedures in which flap reconstruction was required . Either clindamycin phosphate (900 mg) or cefazolin sodium (2 g) therapy was instituted intravenously prior to surgery and continued every 8 hours, for a total of 24 hours . The patients received postoperative follow-up, and the wounds were graded according to the worst condition observed . One hundred cases were evaluated . Fifty-one patients received clindamycin and 49 patients received high doses of cefazolin; wound infection developed in 10 patients (19.6%) and 11 patients (21.6%), respectively . This difference was not statistically significant . The average duration of surgery was approximately 8 hours for both the infected and the noninfected groups of patients . High-dose cefazolin and clindamycin have similar efficacy when administered prophylactically under these circumstances . Reconstruction with free vascularized tissue may aid in reducing postoperative wound infection. J Bacteriol, 1992 May, 174(9), 2958 - 67 abaA, a new pleiotropic regulatory locus for antibiotic production in Streptomyces coelicolor; Fernandez-Moreno MA et al.; Production of the blue-pigmented antibiotic actinorhodin is greatly enhanced in Streptomyces lividans and Streptomyces coelicolor by transformation with a 2.7-kb DNA fragment from the S . coelicolor chromosome cloned on a multicopy plasmid . Southern analysis, restriction map comparisons, and map locations of the cloned genes revealed that these genes were different from other known S . coelicolor genes concerned with actinorhodin biosynthesis or its pleiotropic regulation . Computer analysis of the DNA sequence showed five putative open reading frames (ORFs), which were named ORFA, ORFB, and ORFC (transcribed in one direction) and ORFD and ORFE (transcribed in the opposite direction) . Subcloning experiments revealed that ORFB together with 137 bp downstream of it is responsible for antibiotic overproduction in S . lividans . Insertion of a phi C31 prophage into ORFB by homologous recombination gave rise to a mutant phenotype in which the production of actinorhodin, undecylprodigiosin, and the calcium-dependent antibiotic (but not methylenomycin) was reduced or abolished . The nonproducing mutants were not affected in the timing or vigor or sporulation . A possible involvement of ORFA in antibiotic production in S . coelicolor is not excluded . abaA constitutes a new locus which, like the afs and abs genes previously described, pleiotropically regulates antibiotic production . DNA sequences that hybridize with the cloned DNA are present in several different Streptomyces species. Clin Orthop, 1992 May, (278), 244 - 52 In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads; Adams K et al.; The elution of antibiotics from antibiotic-impregnated polymethylmethacrylate (PMMA) beads was measured in mongrel dogs . The antibiotics, used in mixture with Simplex cement, included cefazolin (Ancef; 4.5 g/40 g cement powder), ciprofloxacin (Cipro; 6 g/40 g powder), clindamycin (Cleocin; 6 g/40 g powder), ticarcillin (Ticar; 12 g/40 g powder), tobramycin (Nebcin; 9.8 g/40 g powder), and vancomycin (Vancocin; 4 g/40 g powder) . After a pneumatic drill was used to dredge a trough in the tibia, five beads were implanted . During the next 28 days, seroma samples and serum samples were taken for antibiotic measurements . On Day 28, the dogs were killed, beads removed, and the seroma, serum, bone, and granulation tissue sampled . The results of the study showed that clindamycin, vancomycin, and tobramycin exhibited good elution characteristics and had consistently high levels in bone and granulation tissue. Fundam Appl Toxicol, 1992 May, 18(4), 499 - 503 Effects of aminoglycoside antibiotics on the auditory brainstem response and post rotatory nystagmus in rats; Yamamoto M et al.; Effects of three aminoglycoside antibiotics, amikacin (AMK), tobramycin (TOB), and gentamicin (GM), on the auditory and vestibular functions were assessed in rats, the most frequently used species in toxicity studies . Chronic electrodes for auditory brainstem response (ABR) recording were implanted on the epidural surface, and those for post rotatory nystagmus (PRN) were implanted at the nictitating membrane and the outer canthus . AMK, TOB, and GM were given intramuscularly twice daily for 3-4 weeks at a daily dose of 350, 150, and 100 mg/kg, respectively . The amplitude of each wave of the ABR was decreased or disappeared in the groups treated with AMK, TOB, and GM . In the PRN, the duration of the nystagmus was decreased in the TOB group and completely lost in the GM group . No abnormality was observed in the PRN in the AMK group . These results were similar to those reported in the ototoxicity studies of these drugs in guinea pigs and indicate that ototoxicity can be evaluated in rats as successfully as in guinea pigs by this procedure. Pathol Biol (Paris), 1992 May, 40(5), 479 - 82 {In vitro sensitivity to antibiotics of genital mycoplasmas isolated in Toulouse . Study of new molecules (macrolides and quinolones)}; Bauriaud R et al.; The minimal metabolism-inhibiting concentrations (MMC) of 11 antibiotics were determined for 40 strains each of M . hominis and U . urealyticum using a terminal color change broth method . All strains were recovered in 1990 . Resistance to tetracycline (MMC greater than 8 mg/l) was found for 12.5% of strains of M . hominis and U . urealyticum, as compared with 5% in 1985 . Rokitamycin was the most active macrolide against M . hominis (MMC 90: 0.06 mg/l) . U . urealyticum strains were susceptible to all the macrolides tested, with the greatest activities being seen for rokitamycin and clarithromycin (MMC 90: 0.06 mg/l and 0.12 mg/l respectively) . Sparfloxacin was the most active quinolone against both species . Human clinical trials designed to evaluate these new molecules for the treatment of mycoplasmal and ureaplasmal genital infections are warranted. Nippon Hinyokika Gakkai Zasshi, 1992 May, 83(5), 627 - 35 {Growth inhibitory effect of a new anticancer antibiotics, kazusamycin A, on human transitional cancer cell lines in vitro}; Sawamura M; Kazusamycin A (KZMA) is a new anticancer antibiotic, which has been proven to have strong anticancer effect and several characteristic features different from currently available anticancer antibiotics . However, there has as yet been no report which had concerned itself with the effect of KZMA on urological cancer . This study was undertaken to determine the inhibitory effects of KZMA on transitional cancer cells in vitro, the augmentation of the inhibitory effect by combining thermal treatment and the effect of KZMA upon DNA distribution . Human transitional cancer cells, KU-1, and T-24 were used as targets . Fifty % inhibitory concentration of KZMA was determined after these cells were exposed to graded concentrations of KZMA for 2 to 48 hours, and to the concentration of KZMA for 2 hours at the temperature of 42 degrees C . Viable cells were counted by dye exclusion assay (DEA) and by tetrazolium-based colorimetric assay (MTT-assay) exposure . KZMA inhibited the growth of the three transitional cancer cells strongly and this inhibitory effect appeared to be depend upon the exposure time and the concentration of KZMA . IC50s after 2-hour exposure at the temperature of 42 degrees C was shown to be decreased to 23 to 87% of that at the temperature of 37 degrees, indicating an augmentation of the inhibitory effect of KZMA by combining thermal treatment . MGH-U1 was the most sensitive to the combination of KZMA and hyperthermia . The cell cycle analysis showed that KZMA had G2-arresting and M-retarding effects, which were different compared with currently available anticancer antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) Nippon Geka Hokan, 1992 May 1, 61(3), 213 - 23 Improved survival in mice with diet-induced pancreatitis treated with new potent protease inhibitor, E-3123 and a broad spectrum antibiotic, cefmetazole; Hirano T et al.; This study was designed to evaluate the infectious factor in the pathogenesis of acute pancreatitis and the effects of a combination therapy with a new potent protease inhibitor, E-3123, and a broad spectrum antibiotic cefmetazole (CMZ) in mice with CDE diet-induced severe acute pancreatitis . Combination therapy with E-3123 and CMZ showed significant protective effects against the high mortality rate, increased serum amylase and ascitic fluid amylase levels, pancreatic amylase and lysosomal enzyme content, plasma endotoxin levels, redistribution of lysosomal enzyme from the lysosomal to the zymogen fraction, lysosomal and mitochondrial fragility, and also improved the histological findings when compared with the E-3123 alone . These results suggest that infections factors play an important role in the development of severe acute pancreatitis and that protease inhibitors in combination with antibiotics may be clinically beneficial. Antibiot Khimioter, 1992 May, 37(5), 38 - 9 {Lymphotropic antibiotic therapy of obstetrical suppurative-septic diseases}; Khodzhaeva AS; The pharmacokinetics and efficacy of gentamicin after its direct and indirect endolymphatic administration were comparatively studied . It was shown that the time course of the blood pharmacokinetics of the antibiotic was almost the same as under the both conditions . Therefore, in many cases the less complicated and more available indirect endolymphatic therapy may replace the direct labor-consuming and traumatic endolymphatic administration of drugs. Antibiot Khimioter, 1992 May, 37(5), 21 - 4 {Use of Hoechst fluorescent probe 33258 for quantitative analysis of intracellular binding of anthracycline antibiotics to DNA}; Egudina SV et al.; The paper deals with development of a procedure for quantitative determination of the share of anthracycline antibiotics bound in cells directly to DNA . A DNA-specific Hoechst fluorescence dye 33258 was used for the purpose . The level of its quenching on DNA correlated with the quantity of the antibiotic bound to it . It was shown that the quenching of the Hoechst fluorescence dye bound to DNA was not due to the dye competition with the antibiotic for the site of bounding on DNA, as was suggested earlier . It was likely to be defined by reabsorption of the radiation by antibiotic molecules. Chem Pharm Bull (Tokyo), 1992 May, 40(5), 1098 - 104 Synthetic studies of carbapenem and penem antibiotics . III . A synthesis of a key intermediate for 1 beta-methylcarbapenem; Sasaki A et al.; We synthesized useful intermediates 5 and 6 for 1 beta- and 1 alpha-methylcarbapenems from 4-carboxy-3-{(R)-1-hydroxyethyl}-2-azetidinone 4 as a starting material by using stereoselective hydrogenation and hydroboration, respectively . A practical synthetic route from 4 to the (3S,4S)-4-{(R)-1-carboxyethyl}-3-{(R)-1-hydroxyethyl}-2-azetidinone derivative 1, a useful intermediate for the synthesis of 1 beta-methylcarbapenem antibiotics, was established. Chem Pharm Bull (Tokyo), 1992 May, 40(5), 1094 - 7 Synthetic studies of carbapenem and penem antibiotics . II . Synthesis of 3-acetyl-2-azetidinones by (2 + 2) cycloaddition of diketene and Schiff bases; Sasaki A et al.; It was found that (2 + 2) cycloaddition reaction of diketene with Schiff bases was effectively promoted by imidazole as a catalyst to afford 3-acetyl-2-azetidinone derivatives 4 . As an application of this new method, a practical asymmetric synthesis of 4 and its conversion into (3S,4S)-4-carboxy-1-(di-p-anisylmethyl)-3-{(R)-1-hydroxyethyl}-2- azetidinone, which is a key intermediate for the synthesis of carbapenem and penem antibiotics, were accomplished. J Antibiot (Tokyo), 1992 May, 45(5), 750 - 5 Mechanism of action of an antifungal antibiotic, RI-331, (S) 2-amino-4-oxo-5-hydroxypentanoic acid; kinetics of inactivation of homoserine dehydrogenase from Saccharomyces cerevisiae; Yamaki H et al.; An antifungal antibiotic (S) 2-amino-4-oxo-5-hydroxypentanoic acid, inhibited the biosynthesis of the aspartate family of amino acids (methionine, isoleucine and threonine) followed by the inhibition of protein biosynthesis in Saccharomyces cerevisiae . This inhibition was effected by impeding the biosynthesis of their common intermediate precursor, homoserine . The inhibition of biosynthesis of homoserine by the antibiotic was attributable to inactivation of homoserine dehydrogenase {EC 1.1.1.3}, which is involved in the conversion of aspartate semialdehyde to homoserine in the metabolic pathway leading to threonine, methionine and isoleucine . Since such enzymic activity is not present in animal cells, the selective antifungal activity of the antibiotic is thus explained. Antibiot Khimioter, 1992 May, 37(5), 5 - 7 {Comparative study of Streptomyces--producer of aminoglycoside antibiotics, monomycin and kanamycin, and the strain 344 obtained by fusion of their protoplasts by the method of restrictive total DNA fingerprinting}; Malanicheva IA et al.; The method of total DNA restriction finger prints was applied to the study of Streptomyces monomycini INA 1465 producing monomycin, Streptomyces kanamyceticus INA K-13 producing kanamycin and strain 344 isolated after fusion of the protoplasts of strain 1465 and K-13, which produced albofungin and chloralbofungin, aminoglycoside antibiotics . For preparing the finger prints of the strains splitting by endonucleases BamHI, PstI, PvuII, and BgIII was used . The finger prints showed that strain 344 was related to the strain of S . monomycini and markedly differed from the strain of S . kanamyceticus . Strain 344 was likely to result from reconstruction (probably 20-kb deletion) of the genome of S . monomycini INA 1465 induced by the preparation and regeneration of its protoplasts . The reconstruction could affect the genome area with localization of the genes involved in monomycin biosynthesis and monomycin resistance genes. J Immunol Methods, 1992 Apr 27, 149(1), 55 - 62 Mycoplasma contamination in human leukemia cell lines . II . Elimination with various antibiotics; Uphoff CC et al.; 19 suspension cell lines were treated with antibiotics for elimination of chronic contamination with mycoplasma . We compared the efficiency, cytotoxicity and cross-resistance of the commercially available antibiotics MRA (Mycoplasma Removal Agent, a quinolone derivative and DNA gyrase inhibitor), Ciprobay (ciprofloxacin, also a quinolone derivative and DNA gyrase inhibitor), and BM-cyclin (a combination of tiamulin, a pleuromutilin derivative, and minocycline, a tetracycline derivative, both inhibitors of protein synthesis on ribosomes) . Contaminants were eliminated in all 19 cell lines by BM-Cyclin . Only 74% of the cell lines were cleared of contamination by both MRA and Ciprobay . Successful treatment was monitored by three mycoplasma detection assays . Cross-resistance was noted between MRA and Ciprobay in four of the five cell lines not cleared by either reagent . This resistance could, however, be overcome by consecutive exposure to BM-cyclin . Employed at the recommended concentrations, the antibiotics did not cause marked cytotoxicity, but the growth of the cells was affected to various degrees by some antibiotics . The elimination of mycoplasma from chronically contaminated cell lines is an effective alternative to other treatment protocols, but is cost-intensive and time-consuming; lasting damaging effects of the treatments on the eukaryotic cells cannot be excluded . Long-term post-treatment monitoring is mandatory, since contaminants may only be suppressed and then recur. Eur J Biochem, 1992 Apr 15, 205(2), 841 - 6 Inhibition of the uptake of oxidized low-density lipoprotein in macrophage J774 by the antibiotic ikarugamycin; Hasumi K et al.; The antiprotozoal antibiotic ikarugamycin was found to significantly inhibit oxidized low-density lipoprotein(LDL)-induced accumulation of cholesteryl ester in macrophage J774 at a concentration over 1-4 microM . Cholesteryl ester synthesis from {14C}oleate in the macrophages was similarly inhibited by the antibiotic, while the synthesis of triacylglycerol and polar lipids was not affected . The internalization of oxidized {125I}LDL in macrophages was reduced to 50% by 2 microM ikarugamycin, while cell-surface binding of oxidized {125I}LDL, lysosomal hydrolysis of the internalized oxidized {125I}LDL and microsomal acyl-coenzyme A:cholesterol acyltransferase was not detectably inhibited by 5 microM ikarugamycin . The results demonstrated that ikarugamycin inhibited cholesteryl ester accumulation in macrophage J774 by specifically inhibiting the uptake of oxidized LDL. Blood, 1992 Apr 15, 79(8), 2022 - 7 Effect of albumin on the inhibition of platelet aggregation by beta-lactam antibiotics; Sloand EM et al.; Platelet aggregation and bleeding time abnormalities are reported in patients receiving beta-lactam antibiotics (beta LAs), although clinical bleeding most frequently occurs in chronically ill, malnourished patients . Although most beta LAs bind to serum albumin, the relative influence of bound versus unbound beta LAs on platelet function is unknown . We examined the effect of beta LAs on the aggregation of gel-filtered platelets from normal subjects and on platelet-rich plasma (PRP) from hypoalbuminemic patients . Therapeutic concentrations of five beta LAs were added to normal platelets at different albumin concentrations (1.5 to 4.5 g/dL) . Inhibition of aggregation by the beta LAs was inversely proportional to the albumin concentration, and most antibiotic-treated samples showed more than 50% inhibition at albumin levels below 2.0 g/dL . When PRPs from hypoalbuminemic patients were incubated with cephalothin, aggregation was completely inhibited, in contrast to samples from patients with normal albumin levels, and this decreased platelet aggregation was partially restored (25% to 75%) by increasing the albumin concentration above 4.0 g/dL . Specific binding of {35S}-benzylpenicillin to normal platelets decreased proportionately as the albumin concentration increased in the range of 1.0 to 5.0 g/dL . The inhibitory effects of beta LAs on platelets in vitro appear to be influenced by albumin concentration . Plasma albumin concentration may influence bleeding in patients receiving beta LAs. Caring, 1992 May, 11(5), 50 - 2, 54, 56 Marketing home i.v . antibiotic therapy to physicians; Bernstein LH; Home intravenous antibiotic therapy (HIVAT) is a safe, efficient, and cost-saving alternative to hospitalization--and the program of choice among patients and their families . Before the full spectrum of benefits can be realized, home infusion companies face the challenge of educating primary care physicians in HIVAT patient selection, antibiotic considerations, and the home care provider team approach. Int Surg, 1992 Apr-Jun, 77(2), 96 - 8 Sensitivity to new generation of antibiotics in biliary surgery; Reiss R et al.; The treatment of septic complications of cholecystectomy patients requires special attention . In a prospective study of 1009 consecutive cholecystectomy patients (including all acute and elective patients, excluding cases of malignancy), we routinely took cultures from the cystic duct and the gallbladder, and checked the strain for sensitivity . Positive cultures were found in 31.4% of the series, the most frequent bacteria being E . coli (50.3%) . The aminoglycosides and the second and third generations of cephaloridins were found more specific for the strains that were cultured . While the new cephaloridins are the first choice for prophylaxis, the combination of aminoglycosides with ampicillin is to be preferred from the medical and cost effective standpoint while the aim is therapeutic. Neurosurg Clin N Am, 1992 Apr, 3(2), 343 - 54 Infections in neurologic surgery . The intraventricular use of antibiotics; Wen DY et al.; Intraventricular antibiotic therapy appears to be a useful treatment modality in those CSF infections in which systemic therapy may fail . Consideration should be given to using this form of treatment when infecting organisms are only sensitive to antibiotics with poor penetration of the CSF (e.g., aminoglycosides and vancomycin) and for cases in which intravenous therapy has failed to sterilize the CSF, toxicity from systemic therapy precludes further increases in dosages, and shunts or other CSF hardware might be expected to reduce the efficacy of systemic therapy by providing a foreign body to harbor organisms . Shunts or reservoirs that are infected may be successfully sterilized with IVT therapy alone or in conjunction with systemic therapy, but this has a lower success rate than cases in which the shunt is removed . There is a wealth of clinical experience with IVT vancomycin and gentamicin that suggests that they are relatively safe . Until more data are available on other aminoglycosides and newer antibiotics, these two agents should be considered the antibiotics of choice for IVT therapy . In situations in which the organism is sensitive to both vancomycin and gentamicin, vancomycin should be used in view of the documented neurotoxicity seen with gentamicin . When gentamicin resistance occurs, amikacin and tobramycin are appropriate alternatives . The high risk of epilepsy with the penicillins and cephalosporins makes them less suited for IVT therapy, although the newer cephalosporins have some promise for IVT therapy . CNS fungal infections can be treated effectively with IVT amphotericin B but with a high risk of significant toxicity . Miconazole appears to be safer than amphotericin B but there is less clinical experience with this drug . Table 1 summarizes the dosages, indications, and toxicity of those antibiotics commonly used for intraventricular administration, which have been reported previously. Pediatr Pulmonol, 1992 Apr, 12(4), 233 - 9 New peripherally inserted midline catheter: a better alternative for intravenous antibiotic therapy in patients with cystic fibrosis; Harwood IR et al.; A study was performed on outpatients with cystic fibrosis (CF) to evaluate the performance of an over-the-needle peripherally inserted midline catheter for the delivery of 2-week courses of antibiotic therapy . The midline is a 7-inch catheter inserted in the antecubital region with the tip located in the axillary region . It is made of a newly developed biomaterial that softens and expands upon contact with body fluids . The hypotheses for the study were that the midline catheter: 1) is useful for intermediate-length therapies; 2) can prevent multiple 3-day conventional peripheral catheter restarts; 3) can prevent or delay the use of more invasive central devices; 4) is comfortable for patients; and 5) is economical . A total of 41 midlines were inserted in 27 patients with an average age and weight of 22 years and 109 pounds, respectively . Prior to this study implanted ports and primarily conventional short peripheral catheters were used to administer I.V . therapy to these patients; fifty percent of these short peripheral catheters failed within 2.6 days . At 2 weeks of dwell, 80% of the midline catheters placed in these patients were still indwelling . Also, 80% of all midline catheter removals were for non-catheter-related reasons . There were no cases of midline catheter phlebitis . In contrast, the phlebitis rates published for peripherally inserted central catheters (PICCs) and conventional short peripheral catheters at 7 days of dwell are 20% and greater than 51% respectively . The midline catheters were comfortable and well liked by most patients and became more economical than conventional peripheral catheters for therapies lasting approximately 6 days through 1 to 2 months.(ABSTRACT TRUNCATED AT 250 WORDS) Z Gastroenterol, 1992 Apr, 30(4), 262 - 3 {Antibiotic-associated segmental hemorrhagic colitis: a case report}; Flueckiger T et al.; Pseudomembranous colitis is a well known complication of antibiotic therapy . Only recently few cases of another form of an antibiotic-associated colitis, the acute segmental haemorrhagic penicillin-associated colitis, have been described . We report another case and point out the importance of early colonoscopy to distinguish the disease from the pseudomembranous colitis. Ophthalmic Surg, 1992 Apr, 23(4), 265 - 8 Intravitreal antibiotics: accuracy of dilution by pharmacists, ophthalmologists, and ophthalmic assi