Arch Dis Child, 1994 Oct, 71(4), 335 - 8 Evaluation of two commercial jet nebulisers and three compressors for the nebulisation of antibiotics; Hung JC et al.; Nebulised antibiotics have been shown to be beneficial in the treatment of lung infections in cystic fibrosis . Studies on the efficiency of nebuliser systems are constantly required in view of the large number of compressor/drug/nebuliser combinations which are possible and the development of new systems and drugs . Six combinations of three commercially available compressors were compared (PortaNeb 50 (Medic-Aid; 5.4-6.1 l/min), Turboneb (Medix; 8.3-9.1 l/min), and CR 60 (Medic-Aid; 7.3-7.8 l/min)) and two jet nebulisers (Microneb III (Lifecare) and System 22 Acorn (Medic-Aid)) for the nebulisation of colomycin, gentamicin, and ciprofloxacin . Aerosol droplet size, nebulisation time, and aerosol output were determined . Turboneb and CR 60 reduced the nebulisation time and produced higher proportions of 'respirable' (< 5 microns diameter) antibiotic aerosols . The residual volume of the Microneb III was lower than that of the System 22 Acorn . It was found that the Turboneb and CR 60, when coupled with either Microneb III or System 22 Acorn, were suitable for the nebulisation of all three antibiotics . Of the equipment tested, Turboneb coupled with Microneb III was the most efficient combination . Even with this combination, only around 50% of the nominal dose was released as respirable aerosol. J Antibiot (Tokyo), 1994 Oct, 47(10), 1145 - 52 Novel antibiotics, amythiamicins . II . Structure elucidation of amythiamicin D; Shimanaka K et al.; The structure of a unique polythiazole-containing cyclic peptide antibiotic, amythiamicin D, was elucidated by chemical degradations and NMR spectral analyses . Acid hydrolysis of amythiamicin D gave one mole of glycine and three new amino acids . Structures of N-acetyl-O-methyl derivatives of these new amino acids were determined by NMR and UV spectral analyses . Connectivities of these amino acids were determined by HMBC experiments. J Antibiot (Tokyo), 1994 Oct, 47(10), 1110 - 5 Nisamycin, a new manumycin group antibiotic from Streptomyces sp . K106 . II . Structure determination and structure-activity relationships; Hayashi K et al.; Nisamycin, a novel manumycin group antibiotic, was isolated from the culture broth of Streptomyces sp . K106 . Structural elucidation of nisamycin was achieved by detailed NMR spectral analyses and comparison of the NMR data of nisamycin with those of other manumycin group antibiotics . The structure was confirmed by chromic acid oxidation . The absolute stereochemistry of nisamycin was determined to be 4R, 5S and 6R from the CD spectra of nisamycin and chromic oxidation of nisamycin . In addition, some structure activity-relationships were examined. J Fam Pract, 1994 Oct, 39(4), 337 - 9 The clinical utility of a day of hospital observation after switching from intravenous to oral antibiotic therapy in the treatment of pyelonephritis; Caceres VM et al.; BACKGROUND . This study was undertaken to investigate the clinical utility of a widespread practice: the 24-hour in-hospital observation period that commonly follows when the treatment of patients hospitalized with acute pyelonephritis is switched from intravenous to oral antibiotics . A preliminary survey of infectious disease specialists confirmed the pervasiveness of this practice and the lack of scientific evidence to support it . METHODS . The clinical utility of in-hospital observation was examined by means of a retrospective chart review of 138 consecutive nonpregnant adult patients who were between the ages of 17 and 65 and had been admitted to a university hospital with a diagnosis of acute pyelonephritis . The progress notes, temperature charts, and laboratory test results were reviewed for any evidence of clinical relapse or adverse reaction to the antibiotic that occurred in the 24-hour period after the switch from intravenous to oral antibiotic therapy . RESULTS . Only two (1%) patients had evidence of clinical relapse within the study period . Five (4%) patients had adverse reactions to their oral antibiotic, none of which were serious . The 95% confidence interval for the percentage of patients who might experience a clinical relapse was from 1% to 5%; for adverse antibiotic reaction, 1% to 8% . CONCLUSIONS . This study shows the limited usefulness of an in-hospital observation period . Savings resulting from avoiding an extra day of hospitalization could amount to millions of dollars annually in the United States. J Bacteriol, 1994 Oct, 176(19), 6107 - 19 Amino acid catabolism and antibiotic synthesis: valine is a source of precursors for macrolide biosynthesis in Streptomyces ambofaciens and Streptomyces fradiae; Tang L et al.; Targeted inactivation of the valine (branched-chain amino acid) dehydrogenase gene (vdh) was used to study the role of valine catabolism in the production of tylosin in Streptomyces fradiae and spiramycin in Streptomyces ambofaciens . The deduced products of the vdh genes, cloned and sequenced from S . fradiae C373.1 and S . ambofaciens ATCC 15154, are approximately 80% identical over all 363 amino acids and 96% identical over a span of the first N-terminal 107 amino acids, respectively, to the deduced product of the Streptomyces coelicolor vdh gene . The organization of the regions flanking the vdh genes is the same in all three species . Inactivation of the genomic copy of the vdh gene in S . fradiae and S . ambofaciens by insertion of a hygromycin resistance (hyg) gene caused loss of the valine dehydrogenase (Vdh) activity, and thus only one enzyme is responsible for the Vdh activity in these organisms . Analysis of the culture broth by bioassay revealed that the vdh::hyg mutants produce an approximately sixfold-lower level of tylosin and an approximately fourfold-lower level of spiramycin than the wild-type S . fradiae and S . ambofaciens strains, while maintaining essentially identical growth in a defined minimal medium with either 25 mM ammonium ion or 0.05% asparagine as the nitrogen source . The addition of the valine catabolite, propionate or isobutyrate, and introduction of the wild-type vdh gene back to each vdh::hyg mutant reversed the negative effect of the vdh::hyg mutation on spiramycin and tylosin production . These data show that the catabolism of valine is a major source of fatty acid precursors for macrolide biosynthesis under defined growth conditions and imply that amino acid catabolism is a vital source of certain antibiotic precursors in actinomycetes. Chest, 1994 Oct, 106(4), 1124 - 8 Allergic reactions to parenteral beta-lactam antibiotics in patients with cystic fibrosis; Pleasants RA et al.; Certain antibiotics, particularly piperacillin, have been reported to be associated with a high incidence of allergic reactions in patients with cystic fibrosis . We initiated a study to determine the relative frequency of allergic reactions, ie, drug-induced fever and rash, to parenteral beta-lactam antibiotics in adult patients with cystic fibrosis . Charts of 111 patients were reviewed for each hospitalization to assess allergic reactions . Of 90 evaluable patients, 26 patients developed one or more allergic reactions to beta-lactam antibiotics . The number of allergic reactions per number of patients receiving specific antibiotics were carbenicillin (4/56), mezlocillin (7/42), piperacillin (11/31), ticarcillin (1/20), cefazolin (0/24), ceftazidime (1/35), imipenem/cilastatin (4/16), and nafcillin (3/36) . The mean time to onset of drug-induced fever or of rash was 9.1 days . As a group penicillins had a higher frequency of allergic reactions than cephalosporins . The frequency of reactions was greatest with acylaminopenicillins (mezlocillin and piperacillin) and imipenem/cilastatin . The results of this study indicate that in addition to piperacillin, mezlocillin and imipenem/cilastatin may be associated with a high incidence of allergic reactions in patients with CF. Aliment Pharmacol Ther, 1994 Oct, 8(5), 495 - 8 Amoxycillin capsules with omeprazole for the eradication of Helicobacter pylori . Assessment of the importance of antibiotic dose timing in relation to meals; Atherton JC et al.; BACKGROUND: Giving antibiotics after meals prolongs their gastric residence time and improves their intragastric distribution . We aimed to see whether this would result in improved eradication of Helicobacter pylori . METHODS: Eighty patients with H . pylori infection were treated with 40 mg omeprazole in the morning for 28 days and amoxycillin 500 mg q.d.s . for days 15-28 . Amoxycillin dosing was randomised to either 1 h before or 10 min after food . Good compliance was pre-defined as missing less than four doses of amoxycillin or two of omeprazole . RESULTS: Amoxycillin dosing after meals was shown not to affect H . pylori eradication rate either when results were analysed on an intention-to-treat basis {amoxycillin before meals successful in 63% (25/40), after in 65% 26/40)} or for good compliers only {before meals 81% (17/21), after 71% (20/28)} . This excludes, with 95% confidence, a benefit of greater than 18% from dosing before, or 23% from dosing after meals . Good compliance, however, was shown to be important, with H . pylori eradication in 76% (37/49) of good compliers compared with 48% (11/23) of others completing the protocol (P < 0.05) . CONCLUSIONS: The timing of antibiotic administration in relation to meals is not important in the treatment of H . pylori infection with this regimen of amoxycillin capsules and omeprazole . Good compliance, is however, an important determinant of treatment success. Pharm Res, 1994 Oct, 11(10), 1405 - 13 Mechanism and kinetics of transcellular transport of a new beta-lactam antibiotic loracarbef across an intestinal epithelial membrane model system (Caco-2); Hu M et al.; Various processes involved in the transcellular transport (TT) of loracarbef (LOR) were studied in the Caco-2 cell monolayer, a cell culture model of the small intestinal epithelium . The results provide support for presence of two AP to BL peptide TT pathways in the intestinal epithelial cell monolayer (Caco-2) . The H+ gradient-dependent pathway (Km = 0.789 mM, and Jmax = 163 pmol/min per cm2) is relatively "high affinity" and "low capacity" compared to H+ gradient-independent pathway (Km = 8.28 mM, and Jmax = 316 pmol/min per cm2) . In addition, TT of LOR in the presence of a H+ gradient was inhibited 77% to 88% (p < 0.05) by 10 mM of cephalexin, enalapril, Gly-Pro and Phe-Pro, while TT of LOR in the absence of a H+ gradient was only inhibited 42% to 48% (p < 0.05) by 10 mM of Gly-Pro and Phe-Pro . Since AP uptake is H+ gradient-dependent and saturable while the BL efflux is mostly nonsaturable and not driven by a H+ gradient, these two transmembrane transport processes must be different, which could be the result of two different peptide carriers . In vivo, these two transport processes must have worked in concert to produce transcellular flux of loracarbef . To explain the differences between kinetic characteristics of AP uptake and TT transport, a cellular pharmacokinetic (PK) model was developed and the results indicate that the PK model appropriately described the kinetics of LOR TT . The use of this PK model may provide an additional advantage to the use of the cell culture model because kinetic parameters at both sides of the intestinal epithelial membrane may be obtained using the same preparation . Taken together, the Caco-2 model system represents an excellent model system for the study of carrier-mediated processes involved in the TT of peptides and peptide-like drugs. Trends Microbiol, 1994 Oct, 2(10), 361 - 6 Origin and molecular epidemiology of penicillin-binding-protein-mediated resistance to beta-lactam antibiotics; Dowson CG et al.; Resistance to beta-lactam antibiotics in some naturally transformable bacterial pathogens has arisen by interspecies recombinational events that have generated hybrid penicillin-binding proteins with reduced affinity for the antibiotics . This type of resistance is of particular concern in pneumococci, in which it is increasing worldwide. Antimicrob Agents Chemother, 1994 Oct, 38(10), 2373 - 9 The endocytic process in CHO cells, a toxic pathway of the polyene antibiotic amphotericin B; Vertut-Doi A et al.; We describe the fate of the polyene antibiotic amphotericin B (AmB) after its interaction with Chinese hamster ovary (CHO) cells . The global uptake of AmB by these cells was measured at 37 degrees C after a 1-h incubation in the presence of 5% fetal bovine serum . It increased with the total concentration of drug and reached a plateau of approximately 1 nmol/mg of cell protein for an external concentration of 25 microM . The same experiment performed at 5 degrees C revealed a drastic decrease in uptake . The distribution of the drug among plasma membranes, endosomes, and lysosomes was then investigated after the separation of the postnuclear fractions by a Percoll gradient . After a 10-min incubation, AmB was found only in the plasma membrane fraction, regardless of the drug concentrations used (5 to 100 microM) . After 60 min, at low drug concentrations (5 and 10 microM) AmB was found to be incorporated mainly in plasma and lysosomal fractions . At high concentrations (50 microM) AmB accumulated in endosomal fractions and plasma membranes . At intermediate concentrations (25 microM) AmB was distributed among the three fractions . When the same experiment was carried out at 5 degrees C, AmB was associated only with the plasma membrane even after 60 min, which was consistent with the absence of endocytotic process at low temperature . The effect of AmB on the endocytic process resulted in the increased uptake of sulforhodamine B, a fluid-phase marker of endocytosis, as well as by the accumulation of sulforhodamine in spots scattered in the cytoplasms of AmB-treated cells, in contrast to the accumulation around the nuclei observed in the control cells . These results are interpreted as indicating that AmB is internalized by the cells through endocytosis and that high concentrations of the drug block the fusion between endosomes and/or the fusion between endosomes and lysosomes. Vet Hum Toxicol, 1994 Oct, 36(5), 437 - 44 Ionophore antibiotic (narasin) poisoning in rabbits; Salles MS et al.; Outbreaks of narasin poisoning in rabbits from several commercial rabbit-raising farms in the state of Parana, Brazil, are reported . Approximately 5,000/35,000 rabbits died after having consumed a pelleted ration to which poultry ration premix had been added . Clinical signs included apathy, anorexia, muscle weakness, impaired walking, diarrhea, respiratory distress, and opistothonus . Gross findings were not remarkable, but varying degrees of degeneration, necrosis and regeneration of skeletal muscles were consistent histopathological features in affected rabbits . Myocardial changes were mild or absent . Thirty ppm of narasin were detected in the ration fed the rabbits . The disease was experimentally reproduced by feeding the suspected ration and by administering narasin po to rabbits. Br J Pharmacol, 1994 Oct, 113(2), 375 - 8 Decrease in calcium currents induced by aminoglycoside antibiotics in frog motor nerve endings; Redman RS et al.; 1 . The effects of the aminoglycoside antibiotics, streptomycin, neomycin and gentamicin were examined on perineural currents and evoked acetylcholine (ACh) release at frog motor nerve endings . 2 . In the standard solutions used previously to measure Ca2+ currents, streptomycin reduced the peak amplitude of the Ca2+ component of the perineural current . 3 . In a solution in which changes in both Ca2+ currents and evoked ACh release can be recorded simultaneously, both Ca2+ currents and evoked ACh release were reduced by aminoglycosides in the potency order neomycin > streptomycin > gentamicin . This potency sequence is similar to that reported previously for these agents as inhibitors of neurally-evoked contractions of mammalian skeletal muscle . 4 . These data suggest that the presynaptic inhibitory effects of aminoglycoside antibiotics at the neuromuscular junction occur as a consequence of a reduction in Ca2+ currents in the motor nerve terminal. Aust Fam Physician, 1994 Oct, 23(10), 1943 - 4 Antibiotic trends in the veteran community; Parkes AJ et al.; The Department of Veterans' Affairs has recently developed improved computer software that enables more thorough analysis of the prescription data in the pharmaceutical database . The department is now in a position to follow prescribing trends in detail for all drugs prescribed for the veteran population . Several drug groups are of interest and on this occasion we have elected to examine the commonly prescribed antibiotics. Contraception, 1994 Oct, 50(4), 319 - 27 Effect of prophylactic antibiotics on morbidity associated with IUD insertion: results of a pilot randomized controlled trial . IUD Study Group; Walsh TL et al.; The efficacy of administering an antibiotic prior to IUD insertion to reduce the risk of introducing an upper genital tract infection during the procedure has not yet been established . Two double-blind randomized studies conducted in Africa comparing a 200 mg prophylactic dose of doxycycline with a placebo did not conclusively identify a reduced risk of post-insertion pelvic inflammatory disease (PID) . A clinical trial of comparable design is currently under way in the US . This multi-site trial will evaluate whether use of an antibiotic prior to insertion reduces the risk of IUD removal for all medical reasons, including upper genital tract infection, within the first three months after insertion . This paper reports on the pilot phase of this study, which was designed to test the protocols and data collection instruments in advance of the full-scale clinical trial . A total of 447 prospective IUD (TCu-380A) users were randomly assigned to receive either a 200 mg dose of doxycycline or a placebo one hour before IUD insertion . 3.6% (8/219) of participants who received the antibiotic had the device removed for medical reasons (infection, bleeding, cramping, etc.) within three months post-insertion compared to 4.5% (10/223) of participants who received the placebo . This reduction in the removal rate was not statistically significant given the limited size of the pilot study (RR = 0.81; 95% CI 0.28-2.29) . Only two subjects, one from each treatment group, met the diagnostic criteria for acute PID . The overall three-month retention rate was 91.8% for the antibiotic group and 89.7% for the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Drug Metab Pharmacokinet, 1994 Oct-Dec, 19(4), 337 - 41 Antibiotic activity in serum following single and repeated oral administration of sodium fusidate in volunteers; Munkholm P et al.; The pharmacokinetics of antibiotic activity were investigated in 10 healthy, female volunteers receiving a single oral dose of sodium fusidate (500 mg) followed after 48 h by repeated oral dosing of 250 mg b.i.d . for 5 consecutive days . By use of turbidimetry, drug-related antibiotic activity in serum was determined and expressed as fusidic acid equivalents . After a single dose and repeated dosing, the peak concentrations were (mean +/- SE): 30 +/- 3 micrograms/ml and 27 +/- 3 micrograms/ml, respectively (NS), and the trough concentration at steady state was 8.4 +/- 1.8 micrograms/ml . The experimental and predicted accumulation ratios were 2.1 +/- 0.1 versus 1.6 +/- 0.2, respectively (P < 0.16) . By use of a model independent method, the terminal elimination half-lives were estimated to be 11 +/- 1 h and 13 +/- 2 h after a single dose and repeated doses, respectively (NS) . The total clearances of antibiotic activity were 2.0 +/- 0.4 l/h after a single dose and 1.6 +/- 0.2 l/h after repeated doses (P < 0.11) . Model dependent pharmacokinetic parameters were also obtained by fitting a two-compartment open model to the median serum concentrations which, with respect to half-life and clearance, gave values close to those observed by use of the model independent approach . Safety-wise, biochemical parameters were within the normal range . However, a statistically significant increase in ASAT and a decrease in leucocytes were observed . The tolerability of the drug was good and only minor adverse events were reported. Appl Biochem Biotechnol, 1994 Oct, 49(1), 1 - 9 Influence of cationic antibiotics on phase behavior of rough-form lipopolysaccharide; Fukuoka S et al.; The rough-form lipopolysaccharide (LPS) interacted with cationic antibiotic polymyxin B and gramicidin S in solution, and showed altered thermotropic phase behavior and viscoelasticity . The phase behavior was measured by differential scanning calorimetry and quartz crystal microbalance (QCM) . Addition of polymyxin B of up to 0.5 mg/mL to the 5.0 mg/mL LPS solution increased gel-to-liquid crystalline phase transition enthalpy (delta H) and raised the transition temperature (tmax) . The further addition of polymyxin B reduced the delta H value . Gramicidin S produced a different effect, whereby a minor addition reduced tmax and delta H value of the LPS . The LPS film on the platinum electrode of the QCM indicated a downward shift of resonant frequency and an upward shift of resonant resistance when in contact with the antibiotic solution . An interpretation of these variations is that the LPS on the QCM electrode changed not only film weight, but also viscoelasticity owing to contact with the antibiotic solution . The different effects between the antibiotics between polymyxin B and gramicidin S on the LPS are induced by the difference of the governing effect . Polymyxin B interacts with the LPS electrostatically, whereas gramicidin S interacts by hydrophobic moieties. J Med Chem, 1994 Sep 16, 37(19), 3191 - 4 Inhibition of topoisomerase I by anthracycline antibiotics: evidence for general inhibition of topoisomerase I by DNA-binding agents; Crow RT et al.; Inhibition of eukaryotic topoisomerase I by daunomycin and structurally modified daunomycin analogues is demonstrated . These studies suggest that binding of the drug to DNA, at low ratios of drug to base pairs of DNA, is sufficient for inhibition that is nonspecific, i.e., inhibition that does not involve the trapping of covalent DNA-topoisomerase I cleavable complexes . Inhibition of numerous DNA-processing enzymes by DNA-binding agents is also implicated. Biochemistry, 1994 Sep 6, 33(35), 10646 - 51 Kinetics, stoichiometry, and identification of the reactive thiolate in the inactivation of UDP-GlcNAc enolpyruvoyl transferase by the antibiotic fosfomycin; Marquardt JL et al.; Fosfomycin {(1R,2S)-1,2-epoxypropylphosphonic acid} has been shown to exert its antibiotic effect through the inhibition of UDP-GlcNAc enolpyruvoyl transferase {Kahan, F . M., et al . (1974) Ann . N.Y . Acad . Sci . 235, 364}, the enzyme responsible for catalyzing the first committed step in bacterial cell wall biosynthesis . Time-dependent inactivation of MurZ by fosfomycin was found to be greatly accelerated by the presence of cosubstrate UDP-GlcNAc but could also be speeded appreciably by the unreactive substrate analog 3-deoxy-UDP-GlcNAc . These results argue against a reaction-based participation of the cosubstrate and suggest that UDP-GlcNAc has a role in influencing active site conformation critical to the inactivation event . A study of the influence of UDP-GlcNAc and fosfomycin on the kinetics of inactivation allowed the determination of dissociation constants for fosfomycin (KF = 8.6 microM) and UDP-GlcNAc (KS = 14 microM), in addition to a limiting inactivation rate constant (k(inact) = 7.4 min-1) at saturating UDP-GlcNAc and fosfomycin concentrations . Mass spectrometry of inactivated MurZ demonstrated an increase in molecular weight of 138, consistent with the covalent addition of a molar equivalent of fosfomycin (136 kDa) . Titration of MurZ with fosfomycin revealed a stoichiometry of 1 molecule of inhibitor per active site when assessed using either enzyme activity or mass spectrometry as an index of modification . Peptide mapping of tryptic digests of fosfomycin-inactivated MurZ revealed modification of a unique 41-mer, the sequence of which revealed that Cys115 was the site of attachment of fosfomycin. Semin Arthroplasty, 1994 Oct, 5(4), 171 - 7 Temporary antibiotic loaded acrylic hip replacement: a novel method for management of the infected THA; Kendall RW et al.; Postoperative infection after hip joint replacement is an uncommon but potentially devastating complication in contemporary orthopaedics . Management in two stages is the more favored approach in North America . This introduces difficulty with patient management in the interval between stages, delays rehabilitation, and introduces technical difficulty during the second stage . A method has been developed whereby a temporary antibiotic-loaded facsimile of the hip is introduced at the first stage, designed to maintain stability of the joint, length of the limb, and mobility of the patient . It has been used in a total of 86 cases to date . The results in 46 cases with a minimum follow-up of 2 years are reviewed in this article . The infection was controlled in 93.5% of cases. Am J Surg, 1994 Sep, 168(3), 288 - 90 Antibiotic overkill of trauma victims? Hadjiminas D, Cheadle WG, Spain DA, Wilson MA, Short A, Starko KM, Harris BJ, Livingston DH, Rodriguez JL. Antibiotic usage was assessed in a prospective, randomized trial of recombinant interferon-gamma (rIFN-gamma) versus placebo for 212 severely injured trauma patients in four university hospitals . All patients were observed until death or discharge from the hospital . We found the number of antibiotics used and their associated costs staggering and difficult to justify, although serious antibiotic-related complications were infrequent . Regular antibiotic administration following severe trauma should be re-evaluated since clinical evidence supports the use of shorter courses for these patients, with presumed similar outcomes and much-reduced expenses. Harefuah, 1994 Sep, 127(5-6), 145 - 8, 216 {National survey of antibiotic use after abdominal surgery}; Karban A et al.; A postal survey of 283 members of the Israeli Association of Surgeons was conducted to determine their current practices as to duration of antibiotic therapy following emergency abdominal operations (response rate 26.5%) . The maximal acceptable length of antibiotic administration after various emergency operations was based on recommendations in the recent literature . By these criteria, about half those responding were using excessive courses of post-operative antibiotics . We conclude that failure to distinguish between contamination, which requires either minimal post-operative administration of antibiotics or none at all, and infection which requires a proper postoperative course, is the main reason for unnecessarily prolonged postoperative use of antibiotics. Ann Gastroenterol Hepatol (Paris), 1994 Sep, 30(4), 168 - 9 {Pseudotumoral aspects of the ileocecal valve in post-antibiotic colitis}; Becheur H et al.; The authors report a case of acute hemorrhagic colitis following amoxicillin therapy, characterized by a tumor-like lesion of the ileo-cecal valve . Clinical symptomatology and endoscopic lesions disappeared within a few days after withdrawal of the antibiotic. J Adv Nurs, 1994 Sep, 20(3), 483 - 90 The extent of parental compliance with timing of administration of their children's antibiotics; Dawson A et al.; Antibiotics are widely prescribed to children, and the responsibility for ensuring adequate administration typically rests with parents . However, compliance with antibiotic medication is generally low, and previous studies often fail to specify the criteria for compliance adequately . In particular, little attention has been paid to accuracy of timing of antibiotic administration outside hospital, even though timing is important in maintaining therapeutic drug levels . The current study examined the self-reports of 75 mothers of their behaviours in administration of antibiotics to their children, with particular attention being paid to the frequency and timing of administration . The study found that, when timing of doses was considered, only seven parents could be considered as fully compliant with dosage instructions, a much lower proportion than indicated in previous studies which applied a more lenient definition of compliance . The implications of this finding are discussed, with particular reference to the role of the nurse and to the comparative usefulness of different definitions of compliance. J AOAC Int, 1994 Sep-Oct, 77(5), 1122 - 31 Simultaneous multiresidue analysis of beta-lactam antibiotics in bovine milk by liquid chromatography with ultraviolet detection and confirmation by electrospray mass spectrometry; Tyczkowska KL et al.; A multiresidue analytical method was developed for the simultaneous determination of amoxicillin, cephapirin, procaine penicillin G, ampicillin, cloxacillin, and ceftiofur in bovine milk . The method involved ultrafiltration of milk diluted with an equal volume of 50% acetonitrile through a 10,000 dalton molecular mass cutoff filter . Separation of these beta-lactam antibiotics from other milk components was performed by ion-paired (octane- and dodecanesulfonate) liquid chromatography using a phenyl column eluted with acetonitrile-water solution . Ultraviolet absorbance of the column effluent was monitored in the 200-350 nm range of a photodiode-array detector . For quantitation, the chromatograms were acquired at lambda 210 nm for penicillin G, ampicillin, and cloxacillin; lambda 230 nm for amoxicillin; and lambda 290 for cephapirin, procaine, and ceftiofur . The limit of detection for the simultaneous determination of these antibiotics was estimated to be 100 ppb . Liquid chromatography/electrospray mass spectrometry could be used to confirm these antibiotics for quantities down to 100 pg entering the mass spectrometer. J Orthop Res, 1994 Sep, 12(5), 737 - 41 Comparison of antibiotic release from polymethylmethacrylate beads and sponge collagen; Becker PL et al.; The rates of elution of tobramycin in vitro were compared for polymethylmethacrylate beads impregnated with the powder form and an alternative biodegradable substance, sponge collagen . The impregnated polymethylmethacrylate beads initially had a lower zone of inhibition, but the rate of release was slow in comparison with that of the impregnated sponge collagen . The sponge collagen delivered a higher dose faster and with a shorter duration than the polymethylmethacrylate beads with the same antibiotic concentration in vitro, but the beads delivered a therapeutic concentration for longer periods . Because it deteriorates rapidly, sponge collagen may be unsatisfactory as an agent of antibiotic delivery in patients who have chronic osteomyelitis; however, it may be useful for patients who have acute trauma with highly contaminated bone or soft tissue, or during hemiarthroplasty revision, to deliver a high local concentration of antibiotic for a short period of time. Br J Dermatol, 1994 Sep, 131(3), 376 - 9 Treatment of Mycobacterium haemophilum infection with an antibiotic regimen including clarithromycin; Darling TN et al.; A patient with rheumatoid arthritis developed ulcerated nodules predominantly on his legs . Skin biopsy and culture demonstrated rheumatoid vasculitis and infection with Mycobacterium haemophilum . Improvement was not seen until clarithromycin was added to his treatment regimen. Dent Update, 1994 Sep, 21(7), 274 - 80 Antibiotics in general practice; Pogrel MA; The human race has had to endure infections for as long as it has been on earth, and has developed efficient natural defence mechanisms to combat them . Modern medicine aims to augment these natural mechanisms, to help speed up resolution of infection and decrease morbidity and mortality. Fam Pract, 1994 Sep, 11(3), 282 - 6 Antibiotics prescription in primary care: a 5-year follow-up of an educational programme; Molstad S et al.; An educational programme on the use of antibiotics for respiratory tract infections (RTIs) in primary care, initiated among district physicians at the Community Health Centre of Hoor, Sweden in 1985, resulted in an overall reduction in prescriptions for antibiotics, particularly broad-spectrum antibiotics . The aim of the present study was to evaluate the long-term effects of the programme on antibiotic prescription patterns at the centre . Since 1985, computerized records have been kept of every consultation at the centre, including details of the attending physician, the patient, diagnosis and type of antibiotic prescribed . Moreover, during a 3-month period in 1991, each pharmacy in the region recorded details of all prescriptions for antibiotics dispensed . Estimated immediately after the programme, the proportion of RTI patients prescribed antibiotics had fallen to 44%, a figure virtually unchanged 5 years later . During the subsequent five-year period, antibiotics dispensed at the pharmacy in Hoor were further reduced from 14.1 to 13.2 defined daily doses 1000 inhabitants-1 day-1 . As compared with district physicians at other community health centres in the region, those at Hoor prescribed more penicillin V (80% of all antibiotic prescriptions) and less broad-spectrum antibiotics . The educational programme, combined with an active interest among district physicians at Hoor in current research into antibiotic usage, has thus wrought enduring changes in the pattern of antibiotic prescription . A probable contributory factor was the district physicians' awareness that the computerized registration of diagnosis and treatment enables prescription patterns to be audited at an individual level. J Pharm Pharmacol, 1994 Sep, 46(9), 718 - 24 Biodegradable controlled antibiotic release devices for osteomyelitis: optimization of release properties; Zhang X et al.; Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(D,L-lactide) (PDLLA) and poly(D,L-lactide-co-epsilon-caprolactone) . These devices have potential application in the treatment of osteomyelitis . The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50% . Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release . The films and melt-extruded cylinders made from poly(D,L-lactide-co-epsilon-caprolactone), low mol . wt poly(D,L-lactide), and a mixture of D,L-lactic acid oligomer and high mol . wt poly(D,L-lactide), did not remain intact during the entire release period . While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110 degrees C . Antibiotic release from high mol . wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid . The antibiotic could only diffuse out through the open ends of the cylinder . Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release . The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0.2, 0.4, 0.7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively . This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Infect Dis, 1994 Sep, 19(3), 522 - 7 Self-administered antibiotic therapy for chemotherapy-induced, low-risk febrile neutropenia in patients with nonhematologic neoplasms; Malik IA et al.; A multicenter prospective nonrandomized trial was conducted to evaluate the efficacy of self-administered oral ofloxacin in the treatment of cancer patients with fever and neutropenia . Patients receiving chemotherapy who either resided far away and were unable to reach the oncology ward within 12 hours of the onset of fever or were unable to afford the expensive inpatient care were eligible for inclusion in the study . Requirements for enrollment included an absolute neutrophil count of < or = 0.5 x 10(9)/L, temperature of > 38 degrees C, and the ability to take oral medications . The patients were instructed to immediately self-administer oral ofloxacin on recognition of fever and to maintain daily telephonic contact with the oncology staff . One-hundred eleven such episodes were evaluable . Neutropenia was mostly of short duration (87% of episodes, < or = 1 week); 92 (83%) of the febrile episodes responded to ofloxacin with resolution of fever and neutropenia (hospitalization was not required) . Two episodes resulted in death before the patients could be brought to the hospital; 17 (15%) did not respond to ofloxacin, and the patients required hospitalization . The conditions of all except one improved with parenteral combination antibiotic therapy . No toxicity was observed, and the cost of therapy was negligible . Treatment with oral ofloxacin may possibly serve as an alternative to hospitalization for those who are otherwise at low risk of morbidity and death. Antimicrob Agents Chemother, 1994 Sep, 38(9), 2197 - 9 Inactivation of the macrolide antibiotics erythromycin, midecamycin, and rokitamycin by pathogenic Nocardia species; Yazawa K et al.; A survey of five Nocardia spp . with respect to susceptibility towards three macrolides (erythromycin, rokitamycin, and midecamycin) showed that the Nocardia spp . have different susceptibility profiles . Most of the resistance was due to the inactivation of the macrolides by phosphorylation, glycosylation, reduction, deacylation, or a combination thereof. Antibiot Khimioter, 1994 Sep-Oct, 39(9-10), 40 - 4 {Prophylactic and therapeutic action of ceftazidime in comparison to that of cefotaxime and combined use of cefotaxime with other antibiotics in experimental plague of albino mice}; Zurabian VA et al.; In a model of experimental plague of albino mice the prophylactic and therapeutic action of ceftazidime by comparison with that of cefotaxime and the combined action of cefotaxime with other antibiotics were studied . The studies showed that the drugs had a high prophylactic and therapeutic action when used in doses of 200 to 400 mg/kg (ceftazidime) and 400 to 800 mg/kg (cefotaxime) . The survival of the animals amounted to 80-100 per cent . The therapeutic effect was defined by the drug dose and the treatment term . When the treatment term was decreased to 3 days, ceftazidime proved to be more advantageous than cefotaxime . When the antibiotic dose was insufficient, the treatment efficacy was shown to depend on the infective dose . The use of cefotaxime in combination with aminoglycosides (gentamicin or sisomicin), rifampicin or doxycycline significantly increased the percentage of the animal survival in comparison to the use of the drugs alone and promoted a rapid elimination of the pathogens in the animals . The combined use of cefotaxime and gentamicin or sisomicin as well as cefotaxime and rifampicin had a synergistic action. Antibiot Khimioter, 1994 Sep-Oct, 39(9-10), 12 - 8 {Dye-sensitized photoisomerization of polyenic macrolide antibiotics}; Shenin IuD et al.; Photoisomerization of levorin A2, a polyenic macrolide, sensitized by various dyes such as thiazines, acridines, xanthenes and phthalocyanines was studied . The use of the dyes made it possible to shift the isomerization process to the visible spectrum region and to increase the quantum yield to 1 . The conditions of the triplet-triplet transfer of the sensitized reaction energy were investigated . By its physio-chemical and biological properties the levorin A2 isomer was identical to the levorin A2 isomer resulting from the direct action on the heptaene chromophore . The dye efficiency was demonstrated in regard to other heptaene antibiotics such as trichomycin and candicidin. Biochem Pharmacol, 1994 Aug 30, 48(5), 881 - 8 Functional expression of intestinal dipeptide/beta-lactam antibiotic transporter in Xenopus laevis oocytes; Tamai I et al.; An intestinal active transport system specific to small peptides and peptide-like drugs such as beta-lactam antibiotics was functionally expressed in Xenopus laevis oocytes after microinjection of messenger RNA (mRNA) derived from rat intestinal mucosal cells . The transport activity was evaluated by measuring the uptake of a tripeptide-like cephalosporin antibiotic, ceftibuten, which has high affinity for the intestinal peptide/H+ co-transporter and is resistant to peptidases . Ceftibuten transport in mRNA-injected oocytes was pH dependent (a proton gradient is the driving force), stereo selective (uptake of the cis-isomer of ceftibuten was about 4-fold higher than that of the trans-isomer), saturable and temperature dependent . Furthermore, various dipeptides showed cis-inhibitory and trans-stimulatory effects on the uptake of ceftibuten by mRNA-injected oocytes, suggesting that ceftibuten and dipeptides are transported by a common carrier protein . These results are in accordance with the functional properties of native proton-coupled peptide transporter previously clarified by studies with isolated intestinal brush-border membrane vesicles and other experimental systems . A protein with a molecular mass of about 130 kDa expressed in the membrane of mRNA-injected oocytes was identified as the transport protein by specific labeling with a photoreactive beta-lactam antibiotic, {3H}benzylpenicillin, followed by SDS-PAGE analysis of the radiolabeled protein . Furthermore, an experiment with mRNA size-fractionated by sucrose density gradient centrifugation indicated that the peptide transporter is encoded by mRNA of between 1.8 and 3.6 kb . These results, obtained using a heterologous gene expression technique, confirm that intestinal absorption of beta-lactam antibiotics occurs through a carrier-mediated mechanism and show that biologically stable beta-lactam antibiotics can be useful probes for molecular analysis of intestinal peptide transporter. Nature, 1994 Aug 25, 370(6491), 659 - 62 Interactions of a small RNA with antibiotic and RNA ligands of the 30S subunit; Purohit P et al.; It is now generally accepted that 16S and 23S ribosomal RNA play important roles in the decoding and peptidyl transferase activities of ribosomes . Despite their complex structures and numerous associated proteins it is possible that small domains of these rRNAs can fold and function autonomously, particularly those that appear devoid of protein interactions . One candidate for such a domain is the decoding region, located near the 3' end of 16S rRNA (Fig . 1a, b) . Consistent with this hypothesis, aminoglycoside antibiotics that interact with the decoding region in 30S subunits interact with other RNAs in the absence of proteins . In addition, certain activities of self-splicing introns, at least superficially, resemble translational decoding . We report here that an oligoribonucleotide analogue of the decoding region interacts with both antibiotic and RNA ligands of the 30S subunit in a manner that correlates with normal subunit function . The activities of the decoding region analogue suggest that the intimidating structural complexity of the ribosome can be, to some degree, circumvented. Ugeskr Laeger, 1994 Aug 22, 156(34), 4829, 4832 - 3 {Treatment of episiotomy wound infections . Incision and drainage versus incision, curettage and sutures under antibiotic cover--a randomized trial}; Christensen S et al.; Conventional, "open" treatment of episiotomy wound infections was compared to incision, curettage and primary suture under antibiotic cover in a prospective, randomized study . During the period 1.5.1986-31.12.1988 there were 4154 vaginal deliveries with episiotomy, of which 20 (0.48%) became infected . Seventeen of these patients consented to enter the study . Median time for healing was 12 days following suture and 19 days after "open" treatment (not significant) . Hospitalization time was the same in the two groups . No re-infections were seen . A need for vaginal plastic repair was found in three of nine of the conventionally treated patients and in none of the patients in the suture group (not significant) . It is concluded that treatment of episiotomy wound infections with incision, curettage and primary suture under antibiotic cover is an attractive, safe ad convenient alternative treatment. Am J Med, 1994 Aug 15, 97(2A), 3 - 8 Physicians, pharmacists, and home infusion antibiotic therapy; Rich D; Home infusion antibiotic therapy has been proven effective, safe, and economical for a variety of infectious diseases . Programs for home infusion have been established in hospitals, home care companies, and physician offices . These programs utilize the combined efforts of physicians, pharmacists, and nurses and rely heavily on the active participation of the patient to provide quality care for a fraction of the cost of hospital-based infusion . Additionally, given a choice, patients prefer to receive intravenous antibiotic therapy at home . Current reimbursement policies, however, acknowledge neither the economic benefit to be derived from home therapy nor patient preference for this mode of intravenous antibiotic therapy. South Med J, 1994 Aug, 87(8), 805 - 7 Antibiotic allergy: inaccurate history taking in a teaching hospital; Absy M et al.; To evaluate the accuracy of allergy histories obtained by interns, residents, and ward attending physicians, we compared physician-charted allergy histories with our own concurrently performed histories over a 2-month span for all general medicine and surgery patients admitted to a 615-bed suburban teaching hospital . We found 100% agreement between investigator and charted histories for all 318 (88%) of 363 charts identifying no known allergy . We disagreed with 23 (50%) of 46 allergies documented in the charts of the remaining 45 patients . Concurrent review classified 18 (39%) of these 46 charted allergies as clinically unimportant, and 5 charts (11%) were deemed underclassified . A description of the allergy by the primary physician was documented in only 7 charts (16%) . Inaccurate allergy histories are frequently documented in the medical record . Simple adjustments in history taking and supervision may have important implications for patient care and training. Biotechniques, 1994 Aug, 17(2), 360 - 5 Effect of different antibiotics on efficiency of transformation of bacteria by electroporation; Steele C et al.; We noted large differences in the transformation efficiency of Escherichia coli when different methods were used for transformation . To analyze these observations, the ampicillin and tetracycline resistance plasmid, pBR322, was transformed into HB101 and DH5 alpha E . coli using calcium chloride or electroporation, and the clones containing the plasmids were selected under various conditions . Electroporation yielded around 5 x 10(7) transformants per microgram of plasmid DNA when ampicillin was used for selection, but only 5 x 10(5) transformants per microgram when tetracycline was used . A calcium-chloride method of transformation showed no differences between the two antibiotics . The loss of efficiency of electroporation in the presence of tetracycline was also seen with three tetracycline-related antibiotics and could be blocked by chelating agents . It was also overcome by a 3-h preincubation of the bacteria before exposure to antibiotic . D-Cycloserine showed a selective effect on electroporated bacteria, but Polymyxin-B, chloramphenicol or phosphonomycin did not . The mechanism of inhibition by tetracycline-related antibiotics is not known, but the results show that the recovery of electroporated bacteria may be significantly decreased if these antibiotics are used. Pediatr Infect Dis J, 1994 Aug, 13(8), 686 - 90 Variation in acceptance of common oral antibiotic suspensions; Dagan R et al.; Palatability of oral antibiotic suspensions is important and may be a substantial factor in determining compliance in young pediatric patients . Because no comparative systematic data are available, we undertook the present study to assess the acceptance of and compliance with oral antibiotic suspensions commonly used in Israel . During a 4-month period lists of children receiving oral antibiotic suspensions were obtained from 3 major pediatric clinics, and parents were contacted by telephone 10 to 14 days after initiation of therapy, at which time information on age, sex, main disease, prescribed drugs and duration of treatment was obtained . Information regarding acceptance, side effects and compliance was obtained from 11 questions with graded scores . In the study 546 children received one of the following drugs: amoxicillin (n = 222); cefaclor (n - 142); cefuroxime axetil (n = 107); trimethoprim/sulfamethoxazole (n = 75) . No major differences in background data were noted; more than 50% of each group had acute otitis media . Seventy-three percent of the cefaclor group reported acceptance of the drug with "pleasure" or "without problems" vs . 60, 55 and 20% for amoxicillin, trimethoprim/sulfamethoxazole and cefuroxime axetil, respectively, whereas "resentment" or "refusal" was reported in 11, 16, 26 and 56%, respectively (P < 0.0001) . Mothers reported to be generally "satisfied" or "extremely satisfied" with the drug in 89, 81, 74 and 67% with cefaclor, amoxicillin, trimethoprim/sulfamethoxazole and cefuroxime axetil, respectively, and 85, 77, 73 and 67% of the children, respectively, received the drug for the entire prescribed course (P < 0.001) . Our data demonstrate that marked variations exist in acceptance and compliance of oral antibiotic suspensions with children.(ABSTRACT TRUNCATED AT 250 WORDS) J Antibiot (Tokyo), 1994 Aug, 47(8), 922 - 31 Solution conformation of enopeptin A, a depsipeptide antibiotic, using 2D NMR and restrained molecular dynamics studies; Young JJ et al.; Studies on the solution conformation of the cyclic depsipeptide antibiotic enopeptin A have been carried out using 2D NMR and molecular modelling techniques . The proton resonances of the antibiotic in DMSO-d6 have been assigned by the use of TOCSY and ROESY experiments . The interproton distance information obtained from the ROESY experiments have been used as the basis for elucidating the probable structures in solution . The restrained molecular dynamics technique was applied to calculate the structures in solution, and six resultant structures with fewer distance constraint violations were obtained that satisfy the experimental restraints very well . The conformation of the cyclic moiety of the molecules is well defined whereas the aliphatic chain segment is disordered. J Antibiot (Tokyo), 1994 Aug, 47(8), 917 - 21 Structures of dnacin A1 and B1, new naphthyridinomycin-type antitumor antibiotics; Hida T et al.; Dnacin A1 and B1 were revealed to be new naphthyridinomycin-type antitumor antibiotics with formulae of C20H23N5O4 and C19H24N4O5, respectively . The gross structure of dnacin A1 was elucidated by the spectroscopic analyses . Conversion of dnacin B1 into A1 by treatment with potassium cyanide indicated the presence of an alpha-carbinolamine moiety in dnacin B1 . The relative stereochemistry of dnacins was clarified by analysis of the NOESY spectra. J Antibiot (Tokyo), 1994 Aug, 47(8), 875 - 80 Dorrigocins: novel antifungal antibiotics that change the morphology of ras-transformed NIH/3T3 cells to that of normal cells . III . Biological properties and mechanism of action; Kadam S et al.; The dorrigocins are unique glutarimide antibiotics which were found to reverse the morphology of ras-transformed NIH/3T3 cells from a transformed phenotype to a normal one . The compounds also inhibited the release of yeast mating pheromone, a-factor . The activity of these compounds was not dependent on inhibition of prenylation or protein synthesis . Dorrigocin A was instead found to inhibit the carboxyl methylation in K-ras transformed cells. J Antimicrob Chemother, 1994 Aug, 34 Suppl A, 11 - 8 Antibiotics at the extremes of age: choices and constraints; Lewis DA et al.; Infection is a frequent cause of morbidity and mortality at the extremes of life . Its treatment is complicated by a lack of specificity in the clinical findings and wider range of pathogens than in other patients . For these reasons empirical therapy must cover a wide range of pathogens and yet, because the clinical findings may not even be due to infection, it should be as non-toxic as possible . It is also essential to investigate intensely before therapy so as to stand the best chance of making an aetiological diagnosis and possibly allowing a change to more directed therapy . Neonates in particular, but also the elderly, are susceptible to age-associated antibiotic toxicities, such as those from tetracyclines and chloramphenicol . Polypharmacy in the elderly renders them particularly liable to drug interactions . Both age groups have altered pharmacokinetics of antibiotics, including differences in absorption, distribution and elimination compared with healthy adults, and therapeutic drug monitoring may be needed more frequently as a result. Eur J Clin Microbiol Infect Dis, 1994 Aug, 13(8), 662 - 5 Successful treatment of recurrent cholangitis with antibiotic maintenance therapy; van den Hazel SJ et al.; The impact of antibiotic maintenance therapy on the incidence of biliary tract infection was evaluated in patients with recurrent cholangitis after resection of a malignancy at the hepatic confluence . Thirty-eight of 54 patients (70%) experienced episodes of cholangitis . In 14 of the 38 patients recurrent episodes of cholangitis caused a severe interruption of their daily life . These 14 were selected for antibiotic maintenance therapy . During maintenance therapy six patients experienced no further episodes of cholangitis and five patients a marked decrease in the frequency of episodes, while in three patients no improvement was seen . Antibiotic maintenance therapy can be highly successful in the treatment of recurrent cholangitis after resection of a malignancy at the hepatic hilum. Antibiot Khimioter, 1994 Aug, 39(8), 22 - 6 {Component composition of the pentaene antibiotic roseofungin}; Shenin IuD et al.; The component composition of the pentaene antibiotic roseofungin was studied by the phase reversal high performance liquid chromatography in the Millichrom apparatus . A 62 x 2 mm column filled with the Separon 5 C18 sorbent was employed . The composition of the mobile phase was determined experimentally by testing various solvent mixtures (methanol-water, methanol-acetate buffer, 0.05 M, pH 4.7, acetonitrile acetate buffer) with different contents of the organic solvent under conditions of isocratic and gradient elution . The optimal separation of the complex was achieved with the use of the mixture of acetonitrile and acetate buffer (45:55) as the mobile phase . Roseofungin was detected at 360 nm . The assay of the roseofungin experimental lots showed that roseofungin mainly contained three components with identical UV spectra . Their contents ranged within 8-17, 45-57 and 25-30 per cent respectively . Some of the samples additionally contained minor components whose quantity did not exceed 20 per cent. J Med Chem, 1994 Jul 22, 37(15), 2266 - 73 Computer modeling analysis for enediyne chromophore-apoprotein complex of macromolecular antitumor antibiotic C-1027; Okuno Y et al.; On the basis of the van der Waals and electrostatic potential energy calculations and energy minimization (EM), a model for the apoprotein-chromophore complex of C-1027 has been constructed by docking the apoprotein (Apo-C1027) and the chromophore (C1027-Chr) . The model of the apoprotein-chromophore complex also suggests the most probable stereochemistry of the chromophore (8R,9S,13R,17R), specific interactions between Apo-C1027 and C1027-Chr, and the origin of the stabilization of the chromophore by the apoprotein . The acetylenic bond of C1027-Chr appears to be stabilized by (1) hydrophobic interactions with the bottom of the pocket of Apo-C1027, (2) orbital interaction with Cys36-Cys45 disulfide bond, (3) van der Waals contact with Pro76, and (4) pi-pi stacking with the benzene moiety of the chromophore . In this model, molecular dynamics (MD) simulation of the chromophore indicates that the acetylene bond distance (C2-C7) of the apoprotein-bound chromophore is longer than that of the unbound chromophore. Anal Chem, 1994 Jul 15, 66(14), 2330 - 5 Class-selective collisionally activated dissociation/ion-molecule reactions of 4-quinolone antibiotics; Colorado A et al.; A new combination of collisionally activated dissociation and ion-molecule reactions in a quadrupole ion trap mass spectrometer is developed for the class-selective determination of 4-quinolones, an important group of antibiotics . In this method, collisionally activated dissociation is used to promote dehydration of each protonated quinolone, and the resulting dehydrated fragment ion undergoes an addition reaction with an auxiliary reagent . The auxiliary reagents, including acetone, acetic anhydride, and n-propylamine, have structures that specifically allow formation of a cyclic adduct with the analyte ion . This sequential process is characteristic of a class of analyte molecules that have adjacent carboxylic acid and ketone functional groups anchored on a rigid ring and undergo facile, efficient dehydration. No Shinkei Geka, 1994 Jul, 22(7), 689 - 93 {Brain abscess ruptured into the lateral ventricle: the usefulness of treatment by intraventricular irrigation with antibiotics . A case report}; Sato M et al.; A case is reported of a brain abscess, which ruptured into the lateral ventricle and was treated using intraventricular irrigation with antibiotics . A 37-year-old man was suffering from a headache and high fever . Precontrast CT scan revealed a heterogeneous low density area in the left temporal lobe, and postcontrast CT scan showed a multilobular ring-like enhanced mass . Diagnosed as a brain abscess, intravenous administration of antibiotics was performed . On the sixth day the patient suddenly became drowsy . Postcontrast CT scan revealed an enhanced effect in the left lateral ventricular wall . Drowsiness was attributed to increased intracranial pressure and severe ventriculitis . Bilateral continuous ventricular drainage via the anterior horn of the lateral ventricle was performed . The drainage fluid from the left lateral ventricle was just like pus . Intraventricular irrigation with antibiotics between the bilateral anterior horns of the lateral ventricle, was performed in order to save the patient . The infusion fluid, Lactate Ringer's solution containing Cefazolin sodium, was infused into the right ventricle and CSF-like pus was drained from the left ventricle . The CSF reading gradually improved, and on the 14th day postoperatively irrigation was terminated . The postoperative course was uneventful . The diagnosis, treatment, and prognosis of patients with brain abscesses have improved dramatically as a result of more reliable methods of identifying infecting organisms, more effective antibiotic regimens, the development of microsurgical techniques and CT scan . However, despite these advances, the prognosis for brain abscess ruptured into the ventricle is usually very pessimistic.(ABSTRACT TRUNCATED AT 250 WORDS) J AOAC Int, 1994 Jul-Aug, 77(4), 891 - 5 Improvement of chemical analysis of antibiotics . Part XIX: Determination of tetracycline antibiotics in milk by liquid chromatography and thin-layer chromatography/fast atom bombardment mass spectrometry; Oka H et al.; A precise liquid chromatographic (LC) determination with high sensitivity and a reliable mass spectrometric (MS) confirmation were established for the determination of tetracycline antibiotics (TCs) in milk . The determination of the TCs was based on C18 cartridge cleanup followed by LC separation . Recoveries of TCs from milk fortified at 20 ppb were 73.0-81.8%, and coefficients of variation were 2.6-4.6% . With this method, concentrations of oxytetracycline and tetracycline as low as 10 ppb and chlortetracycline and doxycycline as low as 20 ppb were determined readily . Thin-layer chromatography (TLC)/fast atom bombardment (FAB) MS with a condensation technique was used to confirm TCs in milk . After the C18 cartridge cleanup, separation on a C8 TLC plate, and application of the sample condensation technique, FAB mass spectra were measured . TCs in milk at 50 ppb were reliably confirmed by TLC/FABMS. J AOAC Int, 1994 Jul-Aug, 77(4), 862 - 70 Performance of various tests used to screen antibiotic residues in milk samples from individual animals; Cullor JS et al.; The 10-point Milk and Dairy Beef Quality Assurance Program was developed collaboratively by the National Milk Producers Federation and the American Veterinary Medical Association and is designed to promote and document the responsible use of antibiotics in the dairy industry . One area of emphasis in this program is testing of individual animals for antibiotic residues after a specified post-treatment withdrawal time . We examined the performance of various assay systems on milk samples from individual cows . These assays are used at present on bulk tank milk samples by regulatory agencies, processing plants, producers, and veterinarians to detect the presence of beta-lactam antibiotics . A high proportion of false-positive results was obtained for both the pretreatment milk samples from cows with clinical mastitis and the milk samples obtained 21 days after initial therapy (nonantibiotic and antibiotic) for the treatment of mastitis . A high proportion of false-positive outcomes was obtained from the milk of clinically normal cows that had not received any medication for at least 30 days prior to evaluation . The results indicate a serious problem in the use of some assays that were designed to evaluate residues bulk tank milk samples to analyze samples from individual cows . This error in assay specificity results in the unjustifiable discarding of milk that meets regulatory standards and may be misused to accuse the producer or veterinarian of not adhering to regulatory guidelines . Maintaining a safe, high-quality milk supply is a constant goal of the dairy industry, which must be provided the appropriate tools and techniques to meet this challenge. Biol Mass Spectrom, 1994 Jul, 23(7), 417 - 29 Multi-residue confirmation of aminoglycoside antibiotics and bovine kidney by ion spray high-performance liquid chromatography/tandem mass spectrometry; McLaughlin LG et al.; An ion spray high-performance liquid chromatographic/tandem mass spectrometric (HPLC/MS/MS) method capable of determining the following six aminoglycosides in bovine kidney is presented: spectinomycin, hygromycin B, streptomycin, dihydrostreptomycin, gentamicin C complex and neomycin B . Tobramycin was used as an internal standard . This method uses an improved matrix solid-phase dispersion (MSPD) method for tissue extraction . A gradient HPLC separation was developed with mobile phases consisting of aqueous 20 mM pentafluoropropionic acid and acetonitrile . Protonated molecules served as precursor ions for collision-induced dissociation (CID) and three product ions were chosen for each analyte for selected reaction monitoring (SRM) where possible . A validation study was conducted for the confirmation of dihydrostreptomycin, neomycin B and four major components of the gentamicin C complex through SRM HPLC/MS/MS analysis of negative control, fortified and incurred bovine kidney samples . All of the samples analyzed could be confirmed with ion ratios within 15% of the daily mean of fortified standards and 90% of the samples had ion ratios within 10% . All compounds except spectinomycin could be detected (while monitoring three ions by SRM) in bovine kidney tissue at or below the regulatory level of concern . MSPD recoveries were acceptable with the exception of the 27% value observed for spectinomycin. Infection, 1994 Jul-Aug, 22(4), 271 - 5 A randomized clinical trial of ceftriaxone and teicoplanin versus ceftazidime and teicoplanin as antibiotic therapy in febrile neutropenic cancer patients and bone marrow transplant recipients; Fauser AA et al.; A prospective, randomized clinical trial comparing combination therapy with ceftriaxone and teicoplanin versus ceftazidime and teicoplanin in the treatment of febrile episodes in neutropenic cancer patients and bone marrow transplant recipients was performed . One hundred and two patients were randomized, but two patients were considered unevaluable for efficacy, and three patients were withdrawn due to incorrect randomization . Of the remaining 97 patients, infection resolved without modification of therapy in 31/49 (63%) patients treated with ceftriaxone/teicoplanin versus 27/48 (56%) patients treated with ceftazidime/teicoplanin (P = 0.48) . Of all 97 patients treated therapy was modified in 18/49 (36%) with ceftriaxone/teicoplanin and 21/48 (43%) with ceftazidime/teicoplanin . Nineteen patients treated with ceftriaxone/teicoplanin received netilmicin and 21 patients treated with ceftazidime/teicoplanin also received netilmicin according to the study design (escalation therapy) . When netilmicin was added infection resolved in 78% of patients treated with ceftriaxone/teicoplanin versus 84% of those treated with ceftazidime/teicoplanin . It was concluded that combination therapy with ceftriaxone/teicoplanin is an alternative to combination therapy with ceftazidime/teicoplanin, and has the advantage of once daily administration. Histol Histopathol, 1994 Jul, 9(3), 555 - 61 Ultrastructural localization of calcium in neuromuscular junctions of smooth and skeletal muscles after aminoglycoside antibiotics treatment; Nouhnejad P et al.; Aminoglycoside antibiotics are all capable of producing clinically significant neuromuscular paralysis . Since part of the mechanism of action of these antibiotics at neuromuscular junction is a calcium-dependent inhibition of acetylcholine release, so this experiment was carried out in vitro on both somatic (isolated rat phrenic-nerve hemidiaphragm) and autonomic neuro-effector transmission (guinea-pig ileum) using gentamicin and amikacin, to determine the calcium contents at this level . Electron microscopic observations on gentamycin- and/or amikacin-treated materials, using potassium pyroantimonate method suggest a reduction of internal calcium in nerve terminals of both preparations. Antimicrob Agents Chemother, 1994 Jul, 38(7), 1641 - 3 Macrolide antibiotics protect against endotoxin-induced vascular leakage and neutrophil accumulation in rat trachea; Tamaoki J et al.; We studied the effects of macrolides on lipopolysaccharide (LPS)-induced airway inflammation in the rat tracheal mucosa . Erythromycin and roxithromycin dose dependently inhibited microvascular leakage and neutrophil recruitment induced by LPS . This inhibitory action on vascular permeability was abolished by neutrophil depletion. Gen Pharmacol, 1994 Jul, 25(4), 787 - 93 Effects of anthracycline antibiotic, daunomycin on thymus chromatin: the role of chromosomal proteins; Rabbani A et al.; 1 . We have examined the effect of antitumour antibiotic daunomycin on calf thymus chromatin employing u.v./vis spectroscopic and hydrodynamic techniques . The experiments were undertaken to determine the influence of added drug on DNA-protein complex . 2 . The results show that the binding of drug to chromatin is dose dependent and a DNA to drug ratio below 1:100 leaves small oligonucleotides in the supernatant, however, at higher ratios chromatin occurs aggregation . 3 . Analysis of both the proteins and DNA reveals that daunomycin induces chromatin condensation by cross linking between its components suggesting that chromosomal proteins play a significant role in this process. Clin Pharmacokinet, 1994 Jul, 27(1), 49 - 62 Review of beta-lactam antibiotics in pregnancy . The need for adjustment of dosage schedules; Heikkila A et al.; beta-Lactam antibiotics represent the oldest class of antibiotics used in the treatment of infections, and benzylpenicillin (penicillin G) is still the most commonly used antibiotic agent during pregnancy . There is a number of studies to suggest that the pharmacokinetics of beta-lactam antibiotics are altered during pregnancy, indicating faster elimination of these antibiotics and lowered plasma concentrations . These changes are largely related to the physiological changes taking place in the maternal body . Generally, drugs are used cautiously during pregnancy, and dosages used may sometimes be inadequate . With regards to antibiotic agents, assurance of adequate therapy by applying pharmacokinetic knowledge when dosage schedules are designed should be a major concern so that the pregnancy is protected from the hazards of infection. Pediatr Hematol Oncol, 1994 Jul-Aug, 11(4), 417 - 21 Early discharge of pediatric febrile neutropenic cancer patients by substitution of oral for intravenous antibiotics; Lau RC et al.; In an open, prospective pilot study of pediatric cancer patients, 23 episodes of fever and neutropenia were treated with intravenous and then oral antibiotics . After 72 hours, patients were changed from intravenous to oral antibiotics if the following criteria were met: negative blood cultures, temperature 38.0 degrees C or lower for 24 hours, absolute neutrophil count less than 0.5 x 10(9)/L, and absence of clinical sepsis . Three patients (13%) had recurrent fever . Intravenous antibiotics were reinstituted in two of these three patients, and oral antibiotics were continued in the third . Fever was believed to be related to relapsed leukemia in one of the three patients . No focus of infection was defined in the other two, and both had good clinical outcomes . The study suggests that this approach to therapy is feasible and can be safely used for selected patients who are anticipated to have a short duration of neutropenia. Dent Clin North Am, 1994 Jul, 38(3), 381 - 402 Antibiotic considerations in medically compromised patients; Lockhart PB et al.; This article discusses bacteremias and dental procedures, medical history taking, and risk assessment considerations for specific medical problems . Recommendations for patient management are reviewed also. Br J Surg, 1994 Jul, 81(7), 989 - 91 Minimal antibiotic therapy after emergency abdominal surgery: a prospective study; Schein M et al.; The optimal duration for courses of antibiotic therapy following emergency abdominal surgery was examined . The length of postoperative administration was based on the operative findings of contamination versus infection and the degree of the latter . A total of 163 patients (mean APACHE II score 7) were stratified into four groups: group 1 (60 patients), no postoperative antibiotics; group 2 (32), antibiotic therapy for 24 h; group 3 (48), administration for 48 h; and group 4 (23), antibiotic therapy for 72 h to 5 days . Three patients (2 per cent) died . Wound infection developed in 12 patients (7 per cent) and postoperative intra-abdominal infection in two (1 per cent) . Antibiotics were stopped according to the protocol in 28 patients in spite of continued fever; one developed a subhepatic abscess and three had wound infections . Distinguishing contamination from infection and operative stratification of the latter allowed a successful 'minimal' postoperative antibiotic policy to be employed. Biophys J, 1994 Jul, 67(1), 143 - 52 Cation conductance and efflux induced by polyene antibiotics in the membrane of skeletal muscle fiber; Shvinka N et al.; Cation conductance and efflux induced by polyene antibiotics amphotericin B (AMB), amphotericin B methyl ester (AME), nystatin, mycoheptin, and levorin on frog isolated skeletal muscle fibers and whole sartorius muscles were investigated . Conductance was measured under current-clamp conditions using a double sucrose-gap technique . Cation efflux was studied using flame emission photometry . Some new data were obtained concerning the effects of levorin and mycoheptin on biological membranes . The power dependence of polyene-induced cation transport on antibiotic concentration in muscle membrane was lower than that in bilayers . The decline in the equilibrium conductance caused by polyene removal (except for levorin) was very fast . There was reverse temperature dependence of AMB- and nystatin-induced conductances . Both induced conductance and efflux values demonstrated a correlation with the order of antifungal activities: levorin > AMB, mycoheptin > AME > nystatin, except for AME, which was more potent on yeastlike cells . These effects were interpreted in terms of possible differences in the kinetics of channel formation in biological and model membranes and in light of the role of nonconducting antibiotic forms in biological membranes. Therapie, 1994 Jul-Aug, 49(4), 325 - 31 {Pseudomembranous colitis caused by antibiotic therapy . Results of a survey of the patient material from the praxis of 900 gastroenterologists}; Carbon C et al.; A retrospective study conducted by interviewing French gastroenterologists was performed with the objective of evaluating the incidence and etiology of pseudomembranous colitis in cases where the diagnosis has been confirmed by coloscopy . This study allowed to collect data on 878 pseudomembranous colitis observed by 438 gastroenterologists within 6 months . It shows evidence of the importance of various antibiotics in the etiology of pseudomembranous colitis (89% of the identified cases) . The following is the list of antibiotics or antibiotic classes, in increasing order of their association with the development of pseudomembranous colitis: macrolides which are very rarely associated, a group represented by cefaclor, cefuroxime axetil and cyclins, which are rarely associated, a third group constituted by amoxicillin, ofloxacin and trimethoprim-sulfamethoxazole which appears to be 2 to 3 times more frequently associated than the previous group, and a fourth group of antibiotics, represented by cefixime and the association amoxicillin-clavulanic acid, which is 7 times more frequently associated than antibiotics of the second group. Antibiot Khimioter, 1994 Jul, 39(7), 10 - 4 {A new look at the mechanism of action of antibiotics of the tetracycline series . Tetracyclines as components of radical-generating systems}; Petrenko IuM; Tetracyclines were shown to be able to form radical-generating systems and to affect biological structures at the account of the radical form generation . The radical-generating systems were found to be based on the phenomenon revealed in this study that the tetracyclines catalyzed oxidation of ferrous oxide by oxygen after its binding by these compounds . In the presence of ascorbate the radical formation with the involvement of oxygen could be continuous and accompanied by reduction of ferrous oxide by ascorbate in complex with tetracyclines and its subsequent oxidation as well induced by them . Ca2+ and Mg2+ forming complexes with tetracyclines had no impact on the radical formation . In complex with tetracyclines the ions did not interfere with the tetracycline ability to catalyze oxidation of ferrous oxide after its binding by these compounds . A notion of two functional centres characteristic of tetracyclines was formulated . One of them (chelating) provided the tetracycline binding to Mg2+ and Ca2+ e.g . in ribosomes and the other (toxic) affected the surrounding biological structures by the radical formation. Pneumoftiziologia, 1994 Jul-Dec, 43(3-4), 189 - 95 Reprimun--an antibiotic with large spectrum and immunomodulatory properties; Paunescu E; Reprimun contains an oxyminomethyl rifamycin-SV derivative as the active substance and has a large spectrum antibiotic activity, on Mycobacterium tuberculosis too . Reprimun also shows an inhibitory activity on viral and human lymphocyte reverse transcriptases, an antiproliferative effect on retrovirus, as well as a selective immunomodulator action at the level of TCD4+ lymphocyte . In animal, the toxicity tests demonstrated a good tolerance . In human subject, the drug is quite well tolerated: no severe adverse reactions were noted during and after its administration for 10-12 months . In man, Reprimun administration demonstrated a therapeutical effect in bacterial infections (tuberculosis included), sarcoidosis, immune thrombocytopenia, as well as in Kaposi's sarcoma . The drug is only for oral administration . It is well absorbed at the level of duodenum, achieving a repeated entero-hepatic circuit that provides a prolonged efficient concentration of Reprimun in blood serum . Like many other ansamycin derivatives, Reprimun can be given intermittently (e.g . twice or three times weekly) . In case of antisarcoidosis therapy, Reprimun was applied with good results in 112 supervised cases, including 37 failures of a prior cortisone treatment its administration could be of a high benefit in HIV serum positive persons in which it can prevent both tuberculosis and HIV infection developments. J Thorac Cardiovasc Surg, 1994 Jul, 108(1), 63 - 7 Biochemical and cellular characterization of cardiac valve tissue after cryopreservation or antibiotic preservation; Lang SJ et al.; It has been reported that aortic homografts that have been cryopreserved before transplantation remain viable longer as an allograft than tissue stored at 4 degrees C in an antibiotic solution . In the present study, we tested the hypothesis that storage of cardiac valve tissue by cryopreservation or by antibiotic preservation may alter the metabolic status of the tissue . Initially, we collected aortic valves composed of cardiac tissue, aortic root, and valvular tissue from cadaver donors . These specimens were divided into three equal portions, and one portion was analyzed before storage while the other two parts were stored for 3 weeks at either 4 degrees C in an antibiotic solution or at -196 degrees C in liquid nitrogen . All specimens were examined with regard to the following parameters: tissue structure, tissue viability, cell proliferative capacity, metabolic function, and identification of cell-specific antigens . We found no significant alterations in the structure of any of the three tissue components after antibiotic preservation or cryopreservation; however, cell viability and cell number were decreased in all three groups . All tissue samples grew in culture before storage . When we compared activities of the following organellar marker enzymes--lysosomal acid lipase, plasma membrane 5' nucleotidase, mitochondrial cytochrome oxidase, and microsomal neutral alpha-glucosidase--we observed no major differences between tissues stored by either technique . In addition, we observed no loss of enzymic activity as a result of storage . Finally, when cell lines isolated from each tissue specimen were incubated with monoclonal antibodies against cell-specific antigens in an immunoperoxidase assay, all the cell cultures proved to be endothelial cells . These results suggest that although cardiac valve tissue stored by cryopreservation or by antibiotic preservation retained its normal structure and metabolic capabilities, both storage techniques produced significant decreases in cell numbers and viability . However, only endothelial cells from tissue stored by cryopreservation retained the capacity to proliferate in vitro . These findings have important implications for the function of aortic homografts transplanted after storage. Semin Arthroplasty, 1994 Jul, 5(3), 122 - 36 Two-stage exchange arthroplasty using a functional antibiotic-loaded spacer in the treatment of the infected knee replacement: the Vancouver experience; Masri BA et al.; Two-stage exchange arthroplasty is currently the method of choice in the treatment of the infected knee replacement . The prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) is a temporary, antibiotic-loaded functional prosthesis that is used as an interim spacer in two-stage exchange arthroplasty . In this prospective series, we report on the early results of the use of the PROSTALAC knee spacer in two-stage exchange arthroplasty of infected knees . A total of 24 knees were treated with this prosthesis, and were reviewed at a mean follow-up time of 2.2 years . Infection was controlled in all but 2 knees, for an infection cure rate of 91.7% . The patients' function was improved between stages, and motion was maintained in the majority of cases . The significant complications with the PROSTALAC implant in place were tibio-femoral instability, which was corrected with a design modification, and patellar instability, which continues to be a problem . These complications were transient and were not of any significance after the second stage. Exp Parasitol, 1994 Jun, 78(4), 341 - 51 Toxoplasma gondii: activity of the polyether ionophorous antibiotic nigericin on tachyzoites in cell culture; Couzinet S et al.; Polyether ionophorous antibiotics are widely used prophylactically to prevent coccidiosis in livestock production . The study of the effects of the nigericin on tachyzoites of Toxoplasma gondii clearly demonstrated that very low concentrations of this ionophore (0.05 microgram/ml) were sufficient to inhibit strongly the penetration and totally inhibit the intracellular development of parasites . Both nigericin and epinigericin showed a similar activity against tachyzoite development . However, the activity of abierixicin was 50-fold lower . Such antibiotic concentrations did not seem to affect host cells . Immunofluorescence and electron microscopy showed important changes in the cytology of the antibiotic-treated parasites: they were vacuolated or swollen and were sometimes found burst open, having lost their original shape . The magnitude and the frequency of alterations rose as concentrations in ionophore increased. Microbiology, 1994 Jun, 140 ( Pt 6), 1351 - 8 Hybrid anthracycline antibiotics: production of new anthracyclines by cloned genes from Streptomyces purpurascens in Streptomyces galilaeus; Niemi J et al.; A DNA segment cloned from Streptomyces purpurascens ATCC 25489 close to a region that hybridized to a probe containing part of the actinorhodin polyketide synthase caused S . galilaeus ATCC 31615 to produce new anthracyclines . When transformed with certain sub-clones of this segment, the host produced glycosides of epsilon-rhodomycinone, beta-rhodomycinone, 10-demethoxycarbonylaklavinone and 11-deoxy-beta-rhodomycinone in addition to those of aklavinone, the natural anthracyclines of S . galilaeus . The first two compounds are S . purpurascens products and the other two are novel compounds that conceptually are structural hybrids between S . galilaeus and S . purpurascens products . Three glycosides of one of the novel aglycones, 11-deoxy-beta-rhodomycinone, were purified and found to possess cytotoxic activity against L1210 mouse leukaemia cells . Separate regions of the cloned S . purpurascens DNA are responsible for modification of the S . galilaeus host product at the 10- and 11-positions. Chem Pharm Bull (Tokyo), 1994 Jun, 42(6), 1231 - 7 Purines . LXIII . Syntheses of azepinomycin, an antitumor antibiotic from Streptomyces species, and its 3-beta-D-ribofuranoside and their 8-imino analogues; Fujii T et al.; Three variants of a synthetic route to the antitumor antibiotic azepinomycin (3) from 1-substituted N'-alkoxy-5-formamidoimidazole-4-carboxamidine (type 10) are described . The synthesis started with the monocytes 10a-c and proceeded through the intermediates 11a-c, 12a-c, 13a-c, 14a-c, and 4a, b and 3-beta-D-ribofuranosylazepinomycin (4c) . The benzyl version (series a), including the permutation 14a-->15-->3, was found to produce the antibiotic (3) most efficiently . The starting materials 10a-c were readily prepared from the 9-substituted adenines 7a-c via the N-oxides 8a-c and the 1-alkoxy derivatives 9a-c . The 8-amino analogues (17 and 18) of 3 and 4c were also synthesized from 12a and 12c, respectively. J Craniomaxillofac Surg, 1994 Jun, 22(3), 167 - 76 Combined treatment with antibiotic, heparin and streptokinase--a new approach to the therapy of bacterial osteomyelitis; Bartowski SB et al.; Combined treatment by continuous intravenous infusion of a selected antibiotic and heparin and/or streptokinase was elaborated as a method of causal, systemic treatment of bacterial osteomyelitis . The aim of the combined treatment was to overcome infection and disturbances in the coagulation and fibrinolysis system which lead to impairment of the bone blood supply and its subsequent necrosis as the main factor in the aetiopathology of osteomyelitis . Between 1969 and 1991, combined treatment was introduced in 63 patients with acute onset disease or with chronic osteomyelitis . Osteomyelitis was located in the mandible in 38 patients and in the long bones in 14 patients . Prior to combined treatment, moderate bone surgery was performed in 21 patients, while 31 patients were excluded from surgery . Combined treatment with an antibiotic and heparin (A+H) was performed in 43 patients, and the other 6 patients had infusion of an antibiotic, streptokinase and heparin (A+S+H) . The authors' method of combined treatment offers a new approach and an alternative to routinely-ordered antibiotic therapy and radical surgery, which allow frequent recurrences of the disease, a long-lasting course and severe complications. Laryngorhinootologie, 1994 Jun, 73(6), 331 - 7 {Ototoxicity of locally administered aminoglycoside antibiotics}; Heidemuller B; In 7 children impairment of hearing was observed after local therapy with neomycin and gentamicin because of scalding wounds . In all cases the hearing loss depends on the duration of treatment with the aminoglycoside antibiotics . Deep and well vascularised wounds strikingly enhance the absorption rates of the ototoxic drugs . 3 adults locally treated with aminoglycoside antibiotics (neomycin, framycetin, gentamicin) for ulcera cruris displayed a delayed development of hearing loss . The hearing impairment occurs several weeks after therapy and leads to deafness in severe cases even if the treatment had been discontinued a long time ago . The most relevant factors in preventing such damage are: strictest possible indication, taking into account all contraindications, as well as shortest possible duration of therapy. Arch Dis Child, 1994 Jun, 70(6), 484 - 7 Once daily antibiotic regimen in paediatric oncology; Bouffet E et al.; The feasibility and efficacy of a once daily antibiotic regimen were assessed in children with malignant tumours . Over a 44 month period, 296 febrile episodes were treated with a regimen of once daily ceftriaxone-amikacin (and teicoplanin or vancomycin if the patient had a central line) . The treatment was successful in 272 (92%) episodes without modification of the antibiotic regimen, and only one patient died of uncontrolled sepsis . A once daily antibiotic regimen is therefore feasible and worthwhile in the treatment of febrile episodes in children with cancer. J Antibiot (Tokyo), 1994 Jun, 47(6), 715 - 23 Synthesis and anticandidal activities of optimized analogs of antibiotic Sch 37137; Andruszkiewicz R et al.; Peptide analogues of Sch 37137 the antifungal antibiotic have been synthesized and evaluated in vitro against Candida sp . Di- and tripeptides containing methionine, leucine, norvaline, lysine, glutamic acid and N3-(trans-epoxysuccinamoyl)-L-2,3-diaminopropanoic acid, (EADP) were obtained . Peptides containing (D)-, and (L)-trans-epoxysuccinamic acid were also prepared . All of the analogues examined displayed in general higher anticandidal activity than a mixture of diastereomers of Sch 37137. J Antibiot (Tokyo), 1994 Jun, 47(6), 655 - 67 Chrymutasins: novel-aglycone antitumor antibiotics from a mutant of Streptomyces chartreusis . II . Characterization and structural elucidation; Uchida H et al.; Chrymutasins A, B and C are glycosidic antibiotics produced by a mutant of the chartreusin producer-organism Streptomyces chartreusis . We report here the structure elucidation of these compounds . The sugar moieties involved were determined by comparison with the related chartreusins . The structure of the aglycone, the same in all three compounds, was elucidated by NMR, incorporation studies of labeled compounds and synthesis of derivatives . The chrymutasin aglycone differs from that of chartreusin by a single carbon and an amino group. FEMS Microbiol Lett, 1994 Jun 1, 119(1-2), 175 - 80 Structural changes induced by glycine on Streptomyces antibioticus; Rodicio MR et al.; Germination and vegetative growth of Streptomyces antibioticus in liquid medium with different concentrations of glycine was examined . Both processes proved to be sensitive to the amino acid, being inhibited by 5 and 2.5% glycine, respectively . At concentrations of 5% or more, lysis of the vegetative mycelium occurred . Subinhibitory concentrations of glycine induced structural changes on germinating spores . These included an increase in the number of germ tubes produced by spore, in relation to the control . Moreover, soon after outgrowth the tubes bifurcate, giving rise to germinated spores with a characteristic aspect, and anomalous formation of cross-walls that appear both within the spores and in the newly formed germinative tubes, at or close to the region of outgrowth . The branching effect of glycine was also observed during vegetative growth of S . antibioticus. J Neurol Neurosurg Psychiatry, 1994 Jun, 57(6), 705 - 8 Antibiotic induced meningitis; River Y et al.; Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis . In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis . Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration . The features common to all three patients were myalgia, confusion and low CSF glucose . CSF analysis was not a reliable method to differentiate antibiotic induced meningitis from partially treated bacterial meningitis. Bioorg Med Chem, 1994 Jun, 2(6), 543 - 51 Oxidative coupling of mithramycin and hydroquinone catalyzed by copper oxidases and benzoquinone . Implications for the mechanism of action of aureolic acid antibiotics; Anyanwutaku IO et al.; The copper oxidases human ceruloplasmin and Polyporous anceps laccase catalyze the oxidative coupling of mithramycin (1) and its aglycone chromomycinone (2) with p-hydroquinone to form new mithramycin-hydroquinone (3) and chromomycinone-hydroquinone adducts (4), respectively . Similar adducts could be formed by the nonenzymatic mimic of this reaction using benzoquinone and these aureolic acids in buffer solutions . FABMS of 3 indicated that the hydroquinone moiety was attached to the aureolic acid aglycone . Acid hydrolysis of 3 yielded a compound with the same chromatographic and spectroscopic characteristics as 4 . Structure elucidation of 4 by NMR and MS revealed that the hydroquinone was attached to the C-5 position of the aglycone . NMR evidence indicated that 4 consisted of a mixture of ortho-substituted biphenyl rotamers . The mechanism of the copper oxidase catalyzed adduct formation reaction is presumed to involve radical formation through hydrogen removal at the 8-phenolic position, radical isomerization, and coupling with semiquinone radical also formed during enzymatic and nonenzymatic incubations . Identification of the covalent-hydroquinone adduct provides evidence that aureolic acid antibiotics can be metabolically converted to reactive radical intermediates, and it establishes the C-5 position of aureolic acid as an enzymatically reactive site . Unlike mithramycin, the mithramycin-hydroquinone adducts was inactive in the in vivo P388 leukemic antitumor test system. Int J Biomed Comput, 1994 Jun, 36(1-2), 77 - 85 Computation of drug concentrations in endocardial vegetations in patients during antibiotic therapy; Maire P et al.; The treatment of endocarditis often requires prolonged antibiotic therapy . Individualized drug dosage regimens have made such therapy possible even in patients with impaired renal function . However, the problem of efficacy remains . Especially for aminoglycosides, it would be a useful guide to have at least an approximate idea of the concentration of an antibiotic within an endocardial vegetation . This study was designed to develop software to model the drug concentrations at different layers within spherical vegetations to provide a guide during clinical therapy of patients with endocarditis . A general model describing the diffusion of antibiotics in spheres has now been developed and interfaced with the USC*PACK PC Clinical Programs in order to compute and plot concentrations, within the vegetation, based on the regimen given to the patient and the diffusitivity of the antibiotic into the vegetation . Some preliminary results of this research, which are still in progress, are presented . Diffusion into simulated spherical vegetations has been computed for different treatment regimens for endocarditis: amikacin or netilmicin and vancomycin were given to three elderly patients (3 women, 74, 75 and 92 years old, with initial estimated creatinine clearances of 51, 36, and 31 ml/min/1.73 m2, respectively) . Although Amikacin has a low diffusivity, the concentrations, even in the center of the vegetation, appear to be effective . The effects of various regimens, including a 'once-a-day' aminoglycoside regimen, are presented. Appl Microbiol Biotechnol, 1994 Jun, 41(4), 447 - 55 Ammonium repression of antibiotic and intracellular proteinase production in Penicillium urticae; Rollins MJ et al.; In this study the addition of ammonium ions (5-30 mM) to Penicillium urticae shake-flask cultures before, during and after the onset of polyketide biosynthesis was examined in a time-dependent manner for its repressive effect on metabolites and a marker enzyme of the patulin pathway and on the intracellular proteinases that also appear during the non-growth or idiophase . A study of the effect of ammonium ion addition, showed that both secondary enzyme and proteinase appearance were maximally delayed if the addition was made before the normal 7 h period of derepression/induction . If added during this period the effect of ammonium ions was progressively less . A reduction in the extracellular ammonium ion concentration from 30 to 4 mM appeared to be required to initiate the derepression/induction process . Adding ammonium ions during the appearance of secondary enzymes caused a rapid decrease in specific activity, about 67% for the patulin pathway enzyme and 12% for proteinase . Nitrogen repression exerts a much stronger effect on the expression of polyketide genes as opposed to proteinase genes . Both patulin pathway enzymes and proteinases are subjected to proteolysis, but the proteinases retain much of their activity, whereas the polyketide biosynthetic enzymes do not. Can J Physiol Pharmacol, 1994 Jun, 72(6), 650 - 8 Cation fluxes and cation channels in outer segment membranes of bovine retinal rods: contamination by antibiotics applied to cattle? Lopez-Escalera R, French RJ, Schnetkamp PP. Membrane vesicles were prepared from intact rod outer segments (ROSs) isolated from bovine retinas and were examined for the presence of cation-selective conductances . We performed macroscopic flux measurements in an ensemble of ROS membrane vesicles and single-channel measurements after fusion of ROS membrane vesicles with planar bilayer membranes . Two K(+)-permeable conductances were observed, the well-established cyclic GMP (cGMP) gated channel and an apparently new K+ channel with some unusual properties . Flux and single-channel data showed that the new conductance passed K+, Rb+, and Cs+ equally well but was much less permeable to Na+, Li+ and protons . Single-channel measurements revealed a linear current-voltage relationship and three unitary conductance states of 15, 11, and 8 pS, using symmetric 150 mM KCl solutions . Measured macroscopic K+ fluxes varied considerably among different preparations, suggesting some unknown regulation of the channel; the variability appeared to arise from variation in the channel's open probability, not the unit conductance or the number of channels present . The recorded single-channel events and the selectivity data are remarkably similar to those reported for antibiotic channel-forming ionophore gramicidin . We believe that the variability in both macroscopic permeability experiments and single-channel experiments may reflect a variable contamination with gramicidin applied to the animals as the topical antibiotic V-Sporin. Aviat Space Environ Med, 1994 Jun, 65(6), 551 - 6 Behavior of bacteria and antibiotics under space conditions; Tixador R et al.; We have previously reported an increase of the "resistance" to antibiotics of bacteria during space missions . In the present experiment, we studied the growth of Escherichia coli cultured in vitro in space in the presence of dihydrostreptomycin: tritiated and nontritiated . This experiment was carried out during the STS 42 mission aboard the U.S . Space Shuttle Discovery (IML-1 program) . Cells were cultured in plastic bags and growth was stopped at six different time points by lowering the temperature to 5 degrees C . Several methods were used: viable cell counting by Colony Forming Units; total cell number by optical densitometry; electron microscopy; radioactivity measurements . The investigations show no difference between flight and ground experiments for the cultures without antibiotic . The growth rate with antibiotic was accelerated in flight, the growth yield was not changed, and there were no differences in the ultrastructures . The results suggest some changes in antibiotic binding in space . We did not observe any differences between the cultures developed in flight in the 1-g centrifuge and the cultures placed in the static rack in microgravity. J Chromatogr A, 1994 May 27, 669(1-2), 75 - 80 Determination of tetracycline antibiotics in animal tissues of food-producing animals by high-performance liquid chromatography using solid-phase extraction; Sokol J et al.; A high-performance liquid chromatographic (HPLC) method was developed for the determination of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) residues in bovine and porcine muscles . The method involved the homogenization of the sample in EDTA-McIlvaine buffer with added n-hexane and dichloromethane, centrifugation, precipitation of the supernatant using trichloroacetic acid and filtration . Preconcentration on Separcol SI C18 cartridges improved the clean-up and the recovery of tetracyclines that were separated by HPLC using the optimized mobile phase of 0.01 M oxalic acid-acetonitrile-methanol (45:35:20) on a Spherisorb ODS 2 column (250 x 4 mm I.D.) . UV detection at 360 nm was applied with a detection limit of about 50 ng/g . The diode-array spectra confirmed the applicability of this method to the study of tetracycline residues in carcasses. Biochem Pharmacol, 1994 May 18, 47(10), 1781 - 8 Rhein enhances the effect of adriamycin on mitochondrial respiration by increasing antibiotic-membrane interaction; Floridi A et al.; The effect of the combination of Adriamycin (ADM) with rhein (RH), an anti-inflammatory drug, on the electron flow through site III and IV of the respiratory chain of rat liver mitochondria was investigated . RH, even at high concentrations, does not inhibit either duroquinol (DHQ) oxidation or cytochrome oxidase activity both of which are decreased by ADM in a dose-dependent manner . The analysis of interaction, performed with the isobolar method, shows a strong synergistic effect that cannot be ascribed to increased permeability of the mitochondrial membranes brought about by RH . The mechanism by which RH potentiates the effect of ADM on DHQ oxidation and cytochrome oxidase activity is most likely to be changes induced in the physical status of the inner mitochondrial membrane such as to permit low ADM concentrations to bind and segregate enough cardiolipin to inhibit electron transport through complex III and IV. Biochemistry, 1994 May 17, 33(19), 5947 - 54 C1027 chromophore, a potent new enediyne antitumor antibiotic, induces sequence-specific double-strand DNA cleavage; Xu YJ et al.; C1027, a new macromolecular antitumor antibiotic produced by a Streptomyces strain, shows highly potent cytotoxicity to cultured cancer cells and marked DNA cleaving ability . The structure of its chromophore, responsible for most of the biological activities of the antibiotic, was recently determined and found to contain a nine-membered enediyne . In contrast to other enediyne antibiotics, such as neocarzinostatin, calicheamicin, esperamicin, and recently found kedarcidin, C1027 damages duplex DNA even in the absence of thiols . The DNA damage caused by C1027 includes double-strand breaks, single-strand breaks, and abasic sites . Experiments with plasmid DNA and 32P-end-labeled restriction fragments demonstrated that the chromophore, extracted from the protein-containing holoantibiotic, interacts in the DNA minor groove and cleaves double-helical DNA with a remarkable sequence-selectivity causing direct double-strand breaks . The double-strand cleavage sites, occurring predominantly at CTTTT/AAAAG, ATAAT/ATTAT, CTTTA/TAAAG, CTCTT/AAGAG, and especially GTTAT/ATAAC, consist of five nucleotide sequences with a two-nucleotide 3'-stagger of the cleaved residues (cutting sites are underlined) . The chemical structures of the damaged residues at the GTTAT/ATAAC cleavage site suggest a model in which a C1027-induced double-strand break results from abstraction, by a single molecule of the diradical form of the chromophore, of a C4' hydrogen atom from the A residue of GTTAT and a C5' hydrogen atom from the A of ATAAC on the opposite strand . Single-strand breaks, which are mainly produced at adenylate and thymidylate residues, appear to be separate events presumably resulting from different binding modes of the drug to DNA.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Biochem, 1994 May 15, 222(1), 129 - 35 Purification and characterization of an extracellular enzyme from Streptomyces antibioticus that converts inactive glycosylated oleandomycin into the active antibiotic; Quiros LM et al.; Cell-free extracts from the oleandomycin producer, Streptomyces antibioticus, possess an intracellular glycosyltransferase capable of inactivating oleandomycin by glycosylation of the 2'-hydroxyl group in the desosamine moiety of the molecule {Vilches, C., Hernandez, C., Mendez, C . & Salas, J . A . (1992) J . Bacteriol . 174, 161-165} . Using a four-step purification procedure, we have purified an enzyme activity from the culture supernatants from this organism which is able to release glucose from the inactive glycosylated molecule thus reactivating the antibiotic activity . This enzyme activity appeared in the culture supernatants immediately before oleandomycin is detected . The enzyme (molecular mass 87 kDa) showed a high degree of substrate specificity, not acting on other glycosylated macrolides such as methymycin, lankamycin and rosaramicin which are substrates for the glycosyltransferase . A second activity was detected corresponding to a 34-kDa polypeptide which probably originates from proteolytic cleavage of the larger polypeptide . The 87-kDa polypeptide possibly catalyses the last biosynthetic step in oleandomycin biosynthesis by S . antibioticus. Aten Primaria, 1994 May 15, 13(8), 409 - 14 {Are antibiotics correctly prescribed in primary care?}; Solsona Diaz L et al.; OBJECTIVE . To identify the antibiotic prescriptions and evaluate their suitability for the infectious conditions treated at a Primary Care Centre . DESIGN . A prospective observation study . SETTING . La Mina Primary Care Centre . Sant Adria de Besos (Barcelona) . PATIENTS AND OTHER PARTICIPANTS . The on-demand visits of patients over 14 to the General Medicine and Emergency clinics between June 1991 and May 1992 provided the data through a simple multi-stage random sample . MEASUREMENTS AND MAIN RESULTS . On the basis of the clinical notes, these variables were recorded: age, gender, diagnosis, the antibiotic prescribed and its manner of administration . The indication and choice of treatment was assessed in line with previously established criteria, as well as whether the antibiotic was first-choice in Primary Care . Infections treated in hospital or by specialists, non-bacterial cutaneous infections and Conjunctivitis were excluded . Out of 2,523 people examined, 474 presented infectious conditions (18.8%); the most common of these were infections of the upper respiratory tract (46.4%) and acute Bronchitis (17.3%) . An antibiotic was prescribed in 206 cases (43.3%) . The most used antibiotics were: Amoxicillin (41.5%), Penicillin (19.0%), Cloxacillin (11.2%), Erythromycin (10.2%) and Pipemidic Acid (7.8%) . They were orally taken in 89.4% of cases . 92.3% of the antibiotics were first-choice . Overall fitness of treatment was 86.3% (56.5% unnecessary and non-prescribed treatment; and 29.7% necessary and using the recommended antibiotic) . The least suitable treatment was observed for cases of acute Bronchitis without any risk factors . CONCLUSIONS . Prescriptions are adjusted to the recommendations on antibiotic policy in Primary Care, although less suitable treatment was observed for acute Bronchitis . The importance of applying a methodology based on objective criteria, in order to make a qualitative analysis in studies on the use of medication, is highlighted. Anal Chem, 1994 May 15, 66(10), 1690 - 5 Use of a macrocyclic antibiotic, rifamycin B, and indirect detection for the resolution of racemic amino alcohols by CE; Armstrong DW et al.; Ansamycins are a very specific class of macrocyclic antibiotics of which the rifamycins are among the better known me