Antibiotics

Curr Opin Biotechnol, 1993 Oct, 4(5), 531 - 7
Genetic engineering of Streptomyces to create hybrid antibiotics; Hopwood DA; Over the past year, dramatic developments in the technology for isolating and manipulating genes for polyketide synthases have been reported . Significant progress has been made in understanding the mechanisms by which these complex enzymes generate the carbon chains of the polyketides, a highly versatile class of natural products . With the demonstration of the production of novel metabolites by synthase engineering, the stage is excitingly set for rationally manipulating synthase 'programming' to generate tailor-made carbon chains.

J Chromatogr, 1993 Sep 22, 619(2), 319 - 23
Rapid determination of tetracycline antibiotics in serum by reversed-phase high-performance liquid chromatography with fluorescence detection; Iwaki K et al.; A rapid and accurate determination of tetracycline antibiotics in human serum by reversed-phase high-performance liquid chromatography with fluorescence detection has been developed, based on protein precipitation in serum . Various reagents for precipitation were investigated, and 24% trichloroacetic acid in methanolic solution gave the maximum recovery (at least 94.3%) and interference-free chromatograms of different three tetracyclines . At a concentration of 0.5 micrograms/ml, the precision (relative standard deviation) ranged from 1.12 to 1.94% . In the range 0.04-10.0 micrograms/ml for oxytetracycline and chlorotetracycline and 0.01-10.0 micrograms/ml for tetracycline, linear responses were observed . The detection limits of this method were 10-35 ng/ml for all three antibiotics . The proposed method was applied to the determination of serum concentrations in subjects receiving tetracycline antibiotics.

Biochem Biophys Res Commun, 1993 Sep 15, 195(2), 659 - 66
Specific interaction between a novel enediyne chromophore and apoprotein in macromolecular antitumor antibiotic C-1027; Matsumoto T et al.; The DNA cleavage experiments show that C-1027 chromophore is selectively incorporated into C-1027 apoprotein and is strongly protected by the apoprotein from loss of its DNA cleaving activity . Fluorescence and circular dichroism spectra reveal (1) important participation of tertiary structure of C-1027 apoprotein for the chromophore binding, (2) specific 1:1 binding of C-1027 chromophore to the apoprotein, and (3) significant interaction of the benzoxazine group in the chromophore-apoprotein complex . On the other hand, C-1027 apoprotein does not contribute to sequence-specificity DNA cleavage by C-1027 antibiotics.

J Immunol Methods, 1993 Sep 15, 164(2), 165 - 73
Production of highly specific monoclonal antibodies to monensin and development of a microELISA to detect this antibiotic; Pauillac S et al.; Monensin, a polyether antibiotic of molecular weight 671 Da, was converted into a hemisuccinate and covalently linked to bovine serum albumin via the mixed anhydride method . Using this immunogen, polyclonal anti-monensin antibodies were raised in rabbits and monoclonal antibodies were prepared from mice . The specificity of the anti-monensin antibodies was examined by using several structural analogues as the immunogen and by performing direct binding and competitive microELISA assays on Terasaki plates . Rabbit polyclonal antibodies had a dissociation constant (KD) of 5.5 x 10(-8) M for monensin and reacted with nigericin, an antibiotic structurally related to monensin . In contrast, a mouse monoclonal antibody, 2H8, reacted only with monensin and had a much lower KD = 3 x 10(-8) M for monensin . Monoclonal antibody 2H8 was used to develop a competitive microELISA able to detect as little as 5 ng/ml of monensin in solution which corresponds to 75 pg or 110 fmol of this hapten per Terasaki well.

Cas Lek Cesk, 1993 Sep 13, 132(17), 529 - 31
{Systemic administration of antibiotics in therapy of brain abscesses . Present trends and possibilities}; Kolar M et al.; The authors describe possibilities as regards selection of antibiotics in the general treatment of brain abscesses . They mention the most frequent aetiological agents of the disease in relation to predisposing factors and site . Systemic antibiotherapy along with surgery is considered by the authors decisive in the therapy of these conditions.

Nucleic Acids Res, 1993 Sep 11, 21(18), 4174 - 9
A molecular basis for human hypersensitivity to aminoglycoside antibiotics; Hutchin T et al.; We have investigated the distribution of mitochondrial DNA polymorphisms in a rare maternally transmitted genetic trait that causes hypersensitivity to aminoglycoside antibiotics, in the hope that a characterization of its molecular basis might provide a molecular and cellular understanding of aminoglycoside-induced deafness (AGD) . Here we report that the frequency of a particular mitochondrial DNA polymorphism, 1555G, is associated nonrandomly with aminoglycoside-induced deafness in two Japanese pedigrees, bringing the frequency of this polymorphism to 5 occurrences in 5 pedigrees of AGD, and in 4 of 78 sporadic cases in which deafness was thought to be the result of aminoglycoside exposure; both frequencies are significantly different from the occurrence of this mutation in the hearing population, which was 0 in 414 individuals surveyed . The 1555G polymorphism occurred in none of 34 aminoglycoside-resistant individuals . We propose a specific molecular mechanism for aminoglycoside hypersensitivity in individuals carrying the 1555G polymorphism, based on the three-dimensional structure of the ribosome, in which the 1555G polymorphism favors aminoglycoside binding sterically, by increasing access to the the ribosome cleft.

J Orthop Res, 1993 Sep, 11(5), 627 - 32
In vitro pharmacokinetics of antibiotic release from locally implantable materials; Miclau T et al.; Local deposition of antibiotics has became increasingly popular in the management of open fractures or osteomyelitis, and several substances have been employed as the vehicle for delivery . Although the elution characteristics of some substances have been documented, a comparative study of the characteristics of the commonly used substances could establish the clinical indications for particular vehicles . Cylindrical pellets of uniform size (6 x 4 mm) were prepared from bone graft (BG), demineralized bone matrix (DBM), plaster of Paris (POP), or polymethylmethacrylate (PMMA), with 25 mg of tobramycin/g of substance in each pellet . The pellets were suspended in phosphate buffered saline, and the antibiotic concentration in the buffer was determined at various time intervals by an enzyme immunoassay . BG and DBM eluted 70 and 45% of their antibiotic load by 24 h, and negligible amounts were detected at 1 week; POP released 17% of its load by 24 h, with trace amounts detected at 3 weeks; and PMMA eluted 7% at 24 h, with trace amounts detected for as long as 14 days . These findings suggest that the optimal vehicle for local deposition of antibiotic depends on the clinical setting . BG and DBM may be best employed when brief antibiotic coverage is required (as for acute contaminated open fractures), whereas POP and PMMA may be better suited for long-term coverage (such as for established osteomyelitis).

J Orthop Res, 1993 Sep, 11(5), 619 - 26
Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute; Cornell CN et al.; The model of Norden was used to induce osteomyelitis in the left tibia of New Zealand White rabbits . Twenty-one days following inoculation, the animals had primary debridement and then were randomized into one of three treatment groups . Group I received no additional treatment; in Group II, plain hydroxyapatite beads were packed into the defect; and in Group III, gentamicin crobefat-loaded hydroxyapatite beads were packed into the defect . The animals were observed for 40 days after the primary debridement and then were killed . The intensity of infection was determined by swab cultures and quantitative bacterial cultures of the debrided material . At primary debridement, all of the animals in each group were equally infected . At the time of secondary debridement, only the animals in Group III had a statistically significant reduction in infection (p < 0.001) . In this study, we demonstrated that an antibiotic-loaded osteoinductive ceramic bead can effectively eliminate bacteria from an osteomyelitic cavity.

J Oral Maxillofac Surg, 1993 Sep, 51(9), 982 - 5; discussion 986
Clinical evaluation of antibiotic-supplemented bone allograft; Petri WH 3rd et al.; Antibiotic-supplemented bone allograft (ASBA) was originally developed for treatment of combat-acquired, avulsive defects of the oral and maxillofacial skeleton . Earlier findings in experimental wound models showed that ASBA resulted in significantly improved wound repair of infected osseous defects when compared with conventional treatment . In this study, ASBA was evaluated in paired, comparable, mandibular third molar sockets and compared with the findings following conventional surgical removal . The results of this assessment showed that wound healing was significantly improved with the use of ASBA . Evidence produced by this clinical evaluation of ASBA suggests its potential use for other surgical bone defects when grafting is precluded by the risk of infection as a result of contamination by oral flora.

Vet Q, 1993 Sep, 15(3), 112 - 7
Elimination of aminoglycoside antibiotics in milk following intramammary administration; Moretain JP et al.; The elimination in cow milk of aminoglycoside antibiotic residues (neomycin, dihydrostreptomycin, kanamycin and gentamicin) was studied after intramammary administration of eight drug formulations marketed in France . Quantitative residue analysis was performed by a cylinder plate method . The sensitivity was 0.15 microgram/ml for neomycin, dihydrostreptomycin, kanamycin and 0.025 microgram/ml for gentamicin . The mean elimination periods ranged between 4 and 13 milkings . Several ways of assessing withdrawal times are discussed.

J Parenter Sci Technol, 1993 Sep-Oct, 47(5), 205 - 10
An approach to the determination of endotoxin in anesthetics and antibiotics: use of an ultrafiltration system and enzymatic LAL reaction; Justicia H et al.; An ultrafiltration system is used to obtain an endotoxin-free buffer for the LAL test . The procedure is combined with a kinetic LAL reaction of high sensitivity . This approach allows for the easy determination of endotoxin levels in parenterals with LAL-interfering substances, reducing the maximum valid dilution necessary for use in product development.

J AOAC Int, 1993 Sep-Oct, 76(5), 952 - 6
Solubility of antibiotics used in animal feeds in selected solvents; Salvatore MJ et al.; The solubility of antibiotics used in animal feeds in organic solvents was determined . The solubility data could be used in identification of classes and in some cases individual members of the same class of antibiotics, and in differential step(s) in the analysis of these antibiotics . A universal solvent was developed to extract all antibiotics from animal feeds.

Antimicrob Agents Chemother, 1993 Sep, 37(9), 2027 - 9
Lincosamide antibiotics stimulate dissociation of peptidyl-tRNA from ribosomes; Menninger JR et al.; At nonpermissive temperatures the peptidyl-tRNA hydrolase of pth(Ts) bacterial mutants is inactivated, and cells accumulate peptidyl-tRNA and die . Doses of erythromycin, lincomycin, or clindamycin that inhibited the growth of antibiotic-hypersensitive DB-11 pth+ cells accelerated the killing of DB-11 pth(Ts) cells at nonpermissive temperatures . Erythromycin and lincomycin also stimulated the accumulation of peptidyl-tRNA . Lincomycin and clindamycin stimulated peptidyl-tRNA dissociation from ribosomes.

J Antibiot (Tokyo), 1993 Sep, 46(9), 1421 - 7
CL307-24, a new antibiotic complex from Saccharopolyspora aurantiaca sp . nov . II . Physico-chemical and biological properties; Fabre B et al.; CL307-24I, the main component of the CL307-24 complex produced by Saccharopolyspora aurantiaca sp . nov., was found to be a potent inhibitor of yeast mitochondrial ATPase . CL307-24I displayed a high degree of activity towards some coryneform bacteria and also has been shown to possess an insecticidal activity . Its biological and physico-chemical properties clearly distinguish it from previously known ATPase inhibitors.

Biull Eksp Biol Med, 1993 Sep, 116(9), 272 - 4
{The cellular acid phosphatase activity in yeast-like fungi of the genus Candida exposed to ultrasound, polyene antibiotics and dyes}; Sergeev PV et al.; The activity of one of the lysosomal membrane marker enzymes--acid phosphatase from the Candida yeast fungi on their exposure to ultrasound (US), polyenic antibiotics (amphotericin B and nystatin) dye antiseptics (ethacridine lactate, methylene blue), and their combinations was assayed . The impact of US and the drugs, in particular their combination, was found to be followed by activation of the fungal lysosomal apparatus function and increases in their catabolic processes . The highest rise in lysosomal catabolic activity was found when the polyenic antibiotics were used in combination with US, which reflects the higher damaging effect of this combination against Candida lysosomal membranes than the dyes and of these antibiotics and US alone . The studies provide strong evidence for the preference of the combined use of US and the polyenic antibiotics in candidiasis as a factor enhancing their fungicidal effect against Candida yeast fungi.

Ann Ital Chir, 1993 Sep-Oct, 64(5), 527 - 32
The role of the administration time of prophylactic antibiotic therapy in colorectal cancer surgery: a review of 6,069 patients from 36 randomized clinical trials; Cosimelli M et al.; The aim of the present report was to establish the effectiveness of different prophylactic antibiotic regimens and administration times in colorectal cancer surgery . Six thousand and sixty nine patients from 36 selected randomized clinical trials, published between 1980 and 1989, were reviewed . The occurrence of septic events, isolated bacterial strains, fever and postoperative hospitalization times were also analyzed . The therapeutic schedules that included the perioperative administration of antibiotics provided better results that those that did not (p . less than .0001 for infections both specifically related and unrelated to colorectal surgery) . The number of postoperative administrations did not affect the clinical results, even if the predominant choice was to give more than one administration of antibiotics . A factorial design demonstrated that prolonging the perioperative administrations up to the postoperative period provided statistically significant benefits (p less than .0001) only with regard to the risk of infections that were not specifically related to colorectal surgery.

Biol Pharm Bull, 1993 Sep, 16(9), 908 - 11
Distinct effects of clinically used anthracycline antibiotics on ras oncogene-expressed cells; Tsuchiya KS et al.; Doxorubicin, pirarubicin, and FAD-104, but not aclarubicin or MX 2, flattened the morphology of NIH3T3 cells that had been transformed by human H-ras and K-ras . The effect appeared on almost all cells, as early as 2 d following exposure to the antibiotics at concentrations inhibiting cell growth by 50% or more . The morphological alteration accompanied other normal cell phenotypes, such as the restoration of actin stress fibers, anchorage dependence of cell growth and an increase in nucleoside diphosphate (NDP) kinase activity . NIH3T3 cells transformed by src and other tumor cell lines responded less prominently, if at all.

Biochemistry, 1993 Aug 17, 32(32), 8068 - 74
Structure of the altromycin B (N7-guanine)-DNA adduct . A proposed prototypic DNA adduct structure for the pluramycin antitumor antibiotics; Sun D et al.; Altromycin B belongs to the pluramycin family of antitumor antibiotics, which also includes kidamycin, hedamycin, pluramycin, neopluramycin, DC92-B, and rubiflavin A . These potent antitumor compounds react with DNA in as yet imprecisely determined ways . In the present investigation, we have used gel electrophoresis methods in combination with nuclear magnetic resonance and mass spectrometry to determine the structure of the altromycin B-DNA adduct . High-resolution gel electrophoresis demonstrated that guanine was the reactive base, and N7 was implicated from experiments in which N7-deazaguanine was used in place of guanine in a strand breakage assay . Experiments using supercoiled DNA demonstrated that altromycin B and related drugs intercalated into DNA, which implicated this as a common mechanism for binding of the pluramycin antibiotics to DNA . The altromycin B-guanine adduct was isolated from calf thymus DNA after thermal depurination of the alkylated DNA . Mass spectrometry confirmed that altromycin alkylated DNA through guanine, and 1H- and 13C-NMR was used to confirm the covalent linkage sites between altromycin B and guanine . On the basis of these results, we propose that altromycin B first intercalates into DNA via a threading mechanism, reminiscent of nogalamycin, to insert the disaccharide into the minor groove and position the epoxide in the major groove in proximity to N7 of guanine . Nucleophilic attack from N7 of guanine leads to an acid-catalyzed opening of the epoxide, resulting in the altromycin B-DNA adduct . On the basis of these results, a general mechanism for the interaction of the pluramycin family of antibiotics with DNA is proposed.

Gene, 1993 Aug 16, 130(1), 107 - 16
Hybridization and DNA sequence analyses suggest an early evolutionary divergence of related biosynthetic gene sets encoding polyketide antibiotics and spore pigments in Streptomyces spp; Blanco G et al.; The whiE gene cluster of Streptomyces coelicolor, which is related to gene sets encoding the biosynthesis of polycyclic aromatic polyketide antibiotics, determines a spore pigment . Southern blotting using probes from three different parts of the whiE cluster revealed related gene sets in about half of a collection of diverse Streptomyces strains . A 5.2-kb segment of one such cluster, sch, previously shown to determine spore pigmentation in Streptomyces halstedii, was sequenced . Seven open reading frames (ORFs), two of them incomplete, were found . Six of the ORFs resemble the known part of the whiE cluster closely . The derived gene products include a ketosynthase (= condensing enzyme) pair, acyl carrier protein and cyclase, as well as two of unidentified function . The seventh ORF diverges from the main cluster and encodes a protein that resembles a dichlorophenol hydroxylase . Comparison with sequences of related gene sets for the biosynthesis of antibiotics suggests that gene clusters destined to specify pigment production diverged from those destined to specify antibiotics early in the evolution of the Streptomyces genus.

Nucleic Acids Res, 1993 Aug 11, 21(16), 3671 - 5
A quantitative assay to measure the relative DNA-binding affinity of pyrrolo{2,1-c} {1,4}benzodiazepine (PBD) antitumour antibiotics based on the inhibition of restriction endonuclease BamHI; Puvvada MS et al.; An assay has been developed (restriction endonuclease digestion assay--RED100) based on inhibition of the restriction endonuclease BamHI that is capable of quantitative evaluation of the relative DNA-binding affinity of pyrrolo{2,1-c} {1,4}benzodiazepine (PBD) antitumour antibiotics . This method provides comparable results to those obtained from thermal denaturation and ethidium bromide displacement assays but is much more sensitive, discriminating between molecules of similar structure such as DC-81, iso-DC-81 and neothramycin . The results reveal a trend between relative DNA-binding affinity and in vitro cytotoxicity for the PBDs in two tumour cell lines studied.

Biochem Pharmacol, 1993 Aug 3, 46(3), 542 - 6
Interaction of the orally active dianionic cephalosporin cefixime with the uptake system for oligopeptides and alpha-amino-beta-lactam antibiotics in rabbit small intestine; Kramer W et al.; The uptake of two orally active beta-lactam antibiotics of different chemical structure, the zwitterionic alpha-aminocephalosporin cephalexin and the dianionic carboxymethoxyimino-cephalosporin cefixime, by brush border membrane vesicles obtained from rabbit small intestine and their molecular interaction with the H+/oligopeptide transport system were investigated . The uptake of both compounds was stimulated by an inwardly directed H(+)-gradient with a profound pH-maximum for cephalexin at pH 6outside and pH 7.4inside whereas cefixime uptake was maximal below pH 5outside . Modification of histidyl residues of membrane proteins led to a complete loss of pH dependence of transport of both cephalosporins . The uptake of cephalexin was competitively inhibited by cefixime and dipeptides and vice versa that of cefixime by cephalexin and dipeptides . The uptake of cefixime was trans-stimulated by cephalexin and glycyl-L-proline whereas cephalexin uptake could only be trans-stimulated by glycyl-L-proline, not by cefixime . Photoaffinity labeling with {3H}benzylpenicillin as a direct photoaffinity probe of the H+/oligopeptide transport system demonstrated a direct molecular interaction of both cephalexin and cefixime with this transporter in the pH range of 5-8 . Thermal pretreatment of membrane vesicles inhibited the cephalexin transport system temperature-dependently, whereas cefixime uptake was not inhibited, but stimulated . Taken together we conclude that dianionic cephalosporins like cefixime bind to the transport system shared by oligopeptides and alpha-amino-beta-lactam antibiotics . Their transport across the enterocyte brush border membrane, however, may occur to a significant extent by a different transport system.

Fundam Appl Toxicol, 1993 Aug, 21(2), 164 - 73
Tapetal effect of an azalide antibiotic following oral administration in beagle dogs; Fortner JH et al.; An azalide antibiotic (CP-62,993) was administered at 100 mg/kg by oral gavage once daily for 35 consecutive days to 3 normal Beagle dogs (tapetal) and 3 Beagle dogs lacking a clinically apparent ocular tapetum (atapetal) . The total dose delivered was approximately 100-fold the recommended clinical dose . Bilateral ophthalmoscopic changes were observed in the treated tapetal dogs on Day 36, consisting of mild to moderate tapetal decoloration with loss of the normal color change at the junction with the nontapetal fundus and muting of reflectivity of the normally highly reflective tapetum; treated atapetal and all control tapetal and atapetal dogs had no ophthalmoscopic changes . Microscopic examination of ocular tissue revealed rudimentary tapetal cell layers in the correct location in untreated, clinically atapetal eyes . Tapetal cells from treated tapetal and atapetal dogs were swollen and vacuolated, and contained intracytoplasmic, electron-dense debris but no recognizable tapetal rodlets . Lysosomal lamellar bodies were observed in the retinal ganglion cells of both treated groups and were neither enhanced nor reduced by the presence of a functional tapetum . Necrosis and inflammation were not observed in any ocular tissue . The altered ophthalmoscopic appearance of treated tapetal dogs was not influenced by the retinal changes because any effect on retinal transparency would have been seen in treated atapetal dogs . The decoloration and muting of reflectivity observed clinically in the tapetal fundus of dogs following prolonged exposure to high levels of CP-62,993 result from unique changes within the ocular tapetum itself and cannot be interpreted to be of consequence to nontapetal species including humans.

Cesk Farm, 1993 Aug, 42(4), 173 - 6
{Polyvalent antibiotics in ambulatory practice}; Blahutova A et al.; The present paper analyzes the consumption of antibiotics from the viewpoint of the diagnosis, specialization of the prescribing physician, and the age and sex of the out-patients . The analysis concerns the prescription within two months in a pharmacy at a policlinic . The results are presented according to the frequency of diagnosis, polyvalence of the antibiotics and the specialization of the prescribing physician.

J Parasitol, 1993 Aug, 79(4), 553 - 8
Glycoside antibiotics alone and combined with tetracyclines for prophylaxis of experimental cryptosporidiosis in neonatal BALB/c mice; Fayer R et al.; Glycoside antibiotics including the macrolide antibiotics azithromycin, clarithromycin, and erythromycin and the aminoglycoside paromomycin were administered alone or combined with doxycycline, minocycline, or tetracycline to neonatal BALB/c mice experimentally infected with Cryptosporidium parvum . Glycosides at 100 or 200 mg/kg of body weight and tetracyclines at 50 mg/kg of body weight were dissolved in dimethylsulfoxide (DMSO), which was then diluted with phosphate-buffered saline (PBS) and given orally by gavage . Drugs were administered at 0, 24, 48, and 72 hr postinfection (PI) for prophylaxis . Histologic sections of ileum, cecum, and colon from tissues fixed at 96 hr PI were examined microscopically to determine the number of developing parasites and assign a quantitative score based on infectivity . All groups that received glycosides had significantly (P < 0.01) lower scores than controls that received only DMSO/PBS . A range in efficacy was apparent . None or extremely few parasites were found in paromomycin- and azithromycin-treated groups, whereas few to moderate numbers of parasites were found in erythromycin- and clarithromycin-treated groups . The addition of tetracyclines did not consistently result in significantly lower scores.

Immun Infekt, 1993 Aug, 21(4), 111 - 4
{Antibiotic therapy in pregnancy}; Friese K; Antibiotics are the most frequently prescribed medications in pregnancy, their application and choice should be made according to the highest criteria . Penicillins and cephalosporins can be safely used in pregnancy, however, their side effects such as allergic reactions present a greater therapeutic problem . Tetracyclines, chloramphenicol and quinolones are strictly contraindicated in pregnancy . 5-nitroimidazole derivatives, aminoglycosides and sulfonamides are indicated only in severe infections . Not only the risk of malformation is increased in the embryonic stage, i.e . in the first 8 weeks of gestation, but also at the time of delivery with the use of drugs as sulfonamides, which can cause icterus.

J Med Microbiol, 1993 Aug, 39(2), 147 - 54
The application of flow cytometry to the study of bacterial responses to antibiotics; Gant VA et al.; Experiments were performed to determine whether a modern flow cytometer could be used to study bacterial populations in suspension, with particular reference to their morphological characteristics and their responses to antibiotics . The FACScan, a commercial benchtop flow cytometer fitted with an air-cooled laser, designed primarily for the study of eukaryotic peripheral blood mononuclear cells, yielded reproducible data relating to bacterial shape and internal architecture . It was sensitive enough to detect changes in bacterial morphology on entry into the growth cycle and after exposure to antibiotics . Antibiotic-induced morphological changes affecting subpopulations of bacteria were sufficiently specific to allow differentiation between antibiotics with different cell-wall enzyme targets . Simultaneously, the effect of such antibiotics on the integrity of the outer cell membrane of Escherichia coli was assessed by measurement of the association of the nucleic acid-binding dye propidium iodide with the bacteria . These experiments demonstrated complex patterns of probable cell-wall leakage, related to the modes of action of the antibiotics . The FACScan is a useful and sensitive tool for the study of the morphology and physiology of bacterial populations in suspension, and is especially applicable to the study of antibiotic action.

J Med Microbiol, 1993 Aug, 39(2), 100 - 6
Influence of subinhibitory levels of antibiotics on expression of Escherichia coli lipopolysaccharide and binding of anti-lipopolysaccharide monoclonal antibodies; Nelson D et al.; The expression of Escherichia coli lipopolysaccharide (LPS) and the binding capacity of anti-LPS monoclonal antibodies (MAbs) to E . coli grown in the presence or absence of subinhibitory concentrations of various antibiotics was studied . Four E . coli strains (three clinical blood-culture isolates and an isogenic, non-capsulate mutant of the O18:K1 parent) were grown in the presence of the beta-lactam antibiotic, ampicillin, the aminoglycoside gentamicin, the fluoroquinolone ciprofloxacin and chloramphenicol . The techniques of silver staining, immunoblotting, whole-cell ELISA and flow cytometry were all used to monitor the expression of LPS on the bacteria and the binding of the anti-LPS MAbs . Treatment with ampicillin, chloramphenicol and ciprofloxacin resulted in enhanced binding of anti-core reactive MAbs to most E . coli strains . Overall, treatment with gentamicin produced the least effect on MAb binding . The presence of chloramphenicol decreased the expression of high molecular mass O-antigen or increased the expression of low molecular mass substituted E . coli LPS or both . These results further illustrate that LPS core, especially the inner-core region, becomes more accessible to antibodies when bacteria are grown in the presence of certain antibiotics . Possible synergy between antibodies and antibiotics for treatment of septicaemia and septic shock remains an intriguing possibility.

Jpn J Antibiot, 1993 Aug, 46(8), 736 - 47
{Criteria for clinical evaluation of antibiotics in pediatrics . The purpose and process for establishing the criteria}; Fujii R et al.; This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol . 46, May, 1993 . The Criteria Committee was organized in November 1991 . Four meetings were held to establish the draft criteria . The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787 . When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent" . Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria . However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy.

Eur J Clin Microbiol Infect Dis, 1993 Aug, 12(8), 622 - 5
Computerised calculation of the true costs of antibiotic therapy; Kerr JR et al.; A system for computerised calculation of the drug costs and hidden costs of antibiotic therapy is described . A previously developed method for costing antibiotic therapy was used to quantify hidden costs arising from intravenous administration, labour, serum antibiotic assays, monitoring of haematological and biochemical indices, and disposal of sharp instruments . These calculations were installed into a software system using spreadsheets (Microsoft Excel/Windows) . Cost calculations were simplified as a result of automated calculation with centralised cost updating, a facility for new antibiotics, a facility for atypical regimens, availability to a number of users, password protection and a facility for multiple courses of intravenous antibiotic therapy.

Aliment Pharmacol Ther, 1993 Aug, 7(4), 463 - 6
Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics; McCarthy CJ et al.; Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common . Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse . This study investigates the effect of omeprazole with antibiotics in H . pylori-associated duodenal ulceration . Forty-three patients with endoscopically proven duodenal ulcer and H . pylori entered this study . Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s . and 500 mg tetracycline t.d.s . Four weeks after completing the treatment, 81% (35/43) had a healed duodenal ulcer, and 58% (25/43) had H . pylori eradication . In those who healed, at one year 21 remained H . pylori-negative, 12 had persistent H . pylori infection and 2 had re-infection . The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H . pylori-negative . This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer relapse than omeprazole alone.

Respir Med, 1993 Aug, 87(6), 449 - 54
Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis; Ip M et al.; We studied the changes in sputum neutrophil chemotactic activity (NCA) and elastolytic activity (EA) in acute exacerbations of bronchiectasis before and after treatment with oral antibiotics . Twelve patients who chronically produced sputum were assessed in the stable state, and when they subsequently developed symptoms of acute exacerbations, prior to initiation of antibiotics, during 2 weeks of antibiotics, and at 2 and 6 weeks after stopping antibiotics . NCA was measured using modified Boyden's technique with multiwell chemotaxis chamber, and EA with N-succinyl-trialanine-p-nitroanilide as elastase substrate . All 12 patients had NCA (49.3 +/- 8.69% FMLP response) and EA (50.5 +/- 17.1 mU per 100 microliters) in their sputum in the stable state . At acute exacerbation, there was significant increase in NCA (P < 0.001) and EA (P < 0.05) . All responded clinically after 1 week of antibiotics, and this was associated with a decrease in NCA and EA back to the levels in stable state . A further week of antibiotics did not result in further decline of NCA or EA . Three patients had another acute exacerbation clinically between 2-6 weeks after stopping antibiotics and their NCA and EA rose again . In the other nine patients, both NCA and EA at 2 and 6 weeks post-treatment were similar to pre-exacerbation levels . Our findings suggest that short course antibiotics effectively control the upsurge in inflammatory activity in acute exacerbations, but has little effect on chronic airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

J Hosp Infect, 1993 Aug, 24(4), 309 - 11
Setting standards--antibiotic policies; Gerken A; It is important to choose appropriate topics for audit in order to produce satisfactory results and maintain interest and enthusiasm . A trail of incomplete audit cycles is unhelpful and demoralizing . The audit should be carefully designed and a vital stage is choosing appropriate standards upon which to measure current performance . An agreed policy provides a practical standard against which to audit the use of antibiotics.

J Pharm Pharmacol, 1993 Aug, 45(8), 756 - 8
Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro; Takeyama K et al.; We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro . Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect . The rank order potency of macrolide was roxithromycin > erythromycin >> clarithromycin . The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin . Roxithromycin increased intracellular cAMP concentrations . These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.

Cancer Res, 1993 Jul 15, 53(14), 3336 - 42
Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics; Hinman LM et al.; The calicheamicin family of antitumor antibiotics are capable of producing double-stranded DNA breaks at sub-picomolar concentrations . Their potency suggested that the calicheamicins would be excellent candidates for targeted delivery and a hydrazide prepared from the most potent and abundant of the naturally occurring derivative, gamma 1I, was linked to oxidized sugars on CT-M-01, an internalizing anti-polyepithelial mucin antibody . The conjugates retained the immunoreactivity of the unmodified antibody and were specifically cytotoxic toward antigen positive tumor cells in vitro and in vivo . Hydrazide analogues of less potent calicheamicin derivatives were also prepared and conjugated to CT-M-01 . Comparison of the therapeutic efficacy of the conjugates against the MX-1 xenograft tumor implanted s.c . in nude mice showed that conjugates of derivatives missing the rhamnose, a sugar residue that is part of the DNA binding region of the drug, were not as promising as antitumor therapies . However, conjugates of two derivatives, alpha 3I and N-acetyl-gamma 1I, in which the rhamnose residue is present but the amino sugar residue of the parent drug is either missing or modified, significantly inhibited tumor growth over a 4-fold dose range and produced long-term tumor-free survivors . Sterically hindering methyl groups adjacent to the disulfide in the linker further increased the therapeutic window of these potent conjugates.

FEBS Lett, 1993 Jul 12, 326(1-3), 95 - 100
Retention of native-like structure in an acyclic counterpart of a beta-sheet antibiotic; Maplestone RA et al.; An acyclic derivative of the cyclic peptide antibiotic, ramoplanin, has been prepared . In aqueous solution, two-dimensional NMR spectroscopy indicates that the acyclic form adopts a threshold population of conformers in which at least part of the beta-sheet characteristic of the intact ramoplanin persists . Thus, despite losing the entropic benefit which the macrocycle must lend to beta-sheet formation, the polypeptide chain of the acyclic ramoplanin appears to display an innate tendency to adopt a native-like conformation.

Clin Orthop, 1993 Jul, (292), 210 - 4
Prophylaxis with systematic antibiotics versus gentamicin bone cement in total hip arthroplasty . A ten-year survey of 1,688 hips; Josefsson G et al.; In 1976, nine Swedish orthopedic departments started a prospective, randomized, and controlled study in which the prophylactic effect of systematic antibiotics (SAs) was compared with gentamicin bone cement (GBC) in 1,688 consecutive total hip arthroplasties (THAs) . After ten years, 13 deep infections had occurred in the SA group and nine in the GBC group . The earlier reported significant difference at two and five years in favor of GBC no longer existed . No allergic or toxic reactions have been reported in the GBC group.

J Clin Gastroenterol, 1993 Jul, 17(1), 14 - 7
Are antibiotics useful in the management of nontoxic severe ulcerative colitis?
Peppercorn MA.
Severely ill patients with ulcerative colitis are usually treated with parenteral corticoids . Those with signs of systemic toxicity usually receive antibiotics as well . However, the role of antibiotics in patients without high fever, profound leukocytosis, peritoneal signs or megacolon is not clear . Since 1985, seven patients who were admitted to the hospital with severe ulcerative colitis but without signs of toxicity have received broad spectrum antibiotics . The patients ranged in age from 21 to 65 years: four were male; all were white . Stools for infectious agents were negative . Each patient received intravenous prednisolone at a dose of 60 mg/24 h . After 7 days, each patient continued to have eight to 10 bloody stools per day with low-grade fever and leukocytosis . Institution of broad-spectrum antibiotics was associated with a striking resolution of bloody diarrhea and normalization of temperature . No patient has required colectomy in follow-up of 2-9 years . Whether the antibiotics are treating an undetected pathogen or eliminating non-pathogenic bacteria contributing to the inflammatory process is not clear . I suggest that severely ill patients with ulcerative colitis deserve a trial of antibiotics before being considered failures of medical therapy.

Geburtshilfe Frauenheilkd, 1993 Jul, 53(7), 488 - 91
{Clarithromycin, a new macrolide antibiotic . Effectiveness in puerperal infections and pharmacokinetics in breast milk}; Sedlmayr T et al.; The aims of this study were, to determine the pharmacokinetic parameters of clarithromycin and to study the passage of the drug into breast milk . Twelve patients (age 24 to 38; weight 44 to 83 kg), suffering from puerperal infections, were treated orally with 250 mg clarithromycin b.i.d . for 6 days . Samples of blood and breast milk were taken at timed intervals . The specimens were assayed for clarithromycin and its active metabolite 14-hydroxy-clarithromycin by HPLC and electrochemical detection . Serum concentrations of clarithromycin in the investigated patients were higher than those reported in healthy volunteers . The mean peak concentrations of clarithromycin and 14-hydroxy-clarithromycin in breast milk were about 25%, and 75% respectively of the corresponding serum concentrations . All patients recovered within 2 to 4 days and no drug-associated side effects (eg . gastrointestinal) were noted . Clarithromycin appears to be an appropriate antibiotic for the treatment of puerperal infections and (because of its considerable concentrations in breast milk) for puerperal mastitis as well.

J Antibiot (Tokyo), 1993 Jul, 46(7), 1139 - 44
PC-766B, a new macrolide antibiotic produced by Nocardia brasiliensis . II . Isolation, physico-chemical properties and structure elucidation; Kumagai K et al.; A new macrolide antibiotic, PC-766B, was isolated from the cells of Nocardia brasiliensis SC-4710 by acetone extraction, and purified by gel filtration, silica gel chromatography, HPLC and TLC . The structure of PC-766B was determined by NMR spectral analysis to be a new class of the hygrolidin family antibiotics . PC-766B had a 16-membered macrocyclic lactone ring, a 6-membered hemiketal ring and a 2-deoxy-D-rhamnose moiety . DL-alpha-Tocopherol, known as an antioxidant agent, significantly improved the stability of PC-766B and prevented the decomposition of PC-766B during the storage of the antibiotic.

J Antibiot (Tokyo), 1993 Jul, 46(7), 1076 - 81
Vicenistatin, a novel 20-membered macrocyclic lactam antitumor antibiotic; Shindo K et al.; A new antitumor antibiotic vicenistatin was isolated from the culture broth of Streptomyces sp . HC34 . The structure of vicenistatin was elucidated by NMR spectral analysis . Vicenistatin exhibited antitumor activity against human colon carcinoma Co-3 in the xenograft model.

Int J Biomed Comput, 1993 Jul, 33(1), 65 - 81
Modeling and simulating the evolution of resistance against antibiotics; Massad E et al.; An epidemiological model is proposed for the spread of resistance against antibiotics in populations of bacterial pathogens . The host population, which is assumed to be constant, is divided into three compartments, viz . susceptible, hosts infected by an antibiotic-sensitive strain and hosts infected by a resistant strain . It is further assumed that susceptibles can be infected by either strain and that there is a possibility for cross-infection between hosts infected by the two strains . The rate of cross-infection can be enhanced by mutations or the transfer of plasmids conferring resistance . Equilibrium analysis was performed in order to determine which of the strain 'wins' the competition by the host . It is assumed that the eventual shift in the competition between the two strains is due to treatment by antibiotic (selective pressure).

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 48 - 51; discussion 63-4
Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Health maintenance organization; Miller Z; HMOs can provide economical outpatient parenteral antibiotic therapy that takes advantage of existing nursing and physician staff as well as centralized pharmacy services . Reimbursement problems are nonexistent . Treatment is possible in the home or clinic . In the model presented, the therapeutic program is initiated and supervised by infectious disease specialists.

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 44 - 7; discussion 62-3
Outpatient parenteral antibiotic therapy . Managemnt of serious infections . Part II: Amenable infections and models for delivery . Emergency department and urgent care center; Lindbeck G; Two approaches to outpatient parenteral antibiotic therapy are commonly used in the emergency care setting . One is daily administration of a parenteral antibiotic followed by oral therapy if clinical response has been satisfactory . The other is administration of a single parenteral dose to initiate a course of oral therapy . Both treatment strategies have proved effective in preliminary studies.

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 31 - 5; discussion 59-60
Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Pyelonephritis; Millar LK; Outpatient therapy is currently recommended for women with uncomplicated pyelonephritis, not those with sepsis, renal insufficiency or pathology, or significant underlying disease . Parenteral therapy is usually initiated in the emergency department, followed by oral therapy at home . Pregnant patients are hospitalized, though studies suggest that outpatient therapy may be appropriate.

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 25 - 30; discussion 58-9
Outpatient parenteral antibiotic therapy . Management of serious infections, Part II: Amenable infections and models for delivery . Pelvic inflammatory disease; Sweet RL; Due to its polymicrobial origins and potential for causing infertility and ectopic pregnancy, pelvic inflammatory disease (PID) is a particularly challenging infection to treat . Treatment of mild PID has long been standardized: a single dose of an IM antibiotic followed by oral therapy . Patients with advanced PID requiring long-term therapy may be candidates for outpatient parenteral therapy.

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 20 - 4, discussion 58
Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Pneumonia and chronic lung disease; Trowbridge JF; The need for medical support is the determining factor when selecting patients with acute pneumonia for outpatient therapy . Patients are often too old or too sick for early discharge, but a large subgroup can continue parenteral therapy as outpatients . Other pneumonia patients, as well as patients with infectious flares of chronic lung disease, can be treated with outpatient therapy alone.

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 15 - 9; discussion 57-8
Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Meningitis; Bradley JS; Children with bacterial meningitis are ideal candidates for outpatient parenteral antibiotic therapy; most recover from the acute infection within five days and do not require skilled nursing observation of neurologic status during the entire course of therapy . Before discharge, the child should be afebrile, show a good response to therapy, and demonstrate no neurologic abnormalities.

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 10 - 4; discussion 57
Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Cellulitis; Lindbeck G et al.; Most patients with cellulitis can be managed on an outpatient basis, frequently with a single dose of parenteral antibiotic followed by oral therapy . Cellulitis must first be differentiated from more serious soft tissue infections that require aggressive inpatient therapy and perhaps surgery . Patients with preexisting medical conditions, such as diabetes, need to be carefully followed if treated as outpatients.

Indian J Pediatr, 1993 Jul-Aug, 60(4), 591 - 4
Antibiotic associated colitis; Ahmad SH et al.; It is a prospective study based on 100 consecutive cases of diarrhea following antibiotic therapy admitted to the pediatric services of J.N . Medical College, A.M.U., Aligarh between January to December 1987 . They had C . penicillin (50), chloramphenicol (34), ampicillin (34), gentamicin (34), cephalosporin (4) and cotrimoxazole (4) for 3 days to 3 weeks prior to the onset of diarrhea . Apart from routine and special investigations, naked eye and microscopic examination of stool, its culture for pathogens including Cl . difficile were carried out in all cases . Presence of Cl . difficile cytotoxin was demonstrated by observing the cytopathic . Effect on veru cell culture, 18 grew Cl . difficile (14 cyto toxin positive) . Frequency of fever, vomiting, abdominal distension, dehydration and duration of diarrhea was not different (p > 0.05) in the two groups . Purge rate and presence of mucus and blood in Cl . difficile positive patients was significantly higher (p < 0.05) . Eight Cl . difficile positive (7 cytotoxin+ve) were subjected to endoscopy . Three of them showed P.M . colitis and 2 non specific colitis . Chloromycetin, gentamicin and penicillin were the main culprits responsible for AAC . None of the patients given ampicillin alone suffered from AAC . The mortality was 5%.

Gig Sanit, 1993 Jul, (7), 42 - 3
{Effect of industrial noise and ototoxic antibiotics on ear function in man}; Anichin VF et al.; Fifty workers of the 166 ones examined were occupationally exposed to noise; 26 of them were treated with ototoxic antibiotics . Workers of treated with antibiotics most often (69.2%) developed deterioration of acoustic function.

Biopharm Drug Dispos, 1993 Jul, 14(5), 443 - 54
Toxicokinetic approach for evaluating respiratory depression effect of aminoglycoside antibiotics: species differences in drug susceptibility; Komiya I et al.; The respiratory depression effect of aminoglycoside antibiotics was studied by a toxicokinetic approach, and species differences in drug susceptibility were elucidated based on plasma concentrations . An allometric relationship was obtained between total body clearance of arbekacin, a novel aminoglycoside antibiotic, and animal body weight . The power was 0.714, less than unity, which means smaller animals have higher ability to eliminate the drug from the body and need higher doses to attain a certain steady-state plasma concentration . When the infusion rate of arbekacin was altered, the total dose required to cause the toxicologic endpoint for respiratory depression (60 per cent loss of respiratory rates) changed greatly, but the plasma concentration of arbekacin at the toxicologic endpoint remained at almost a constant level . The concentration at the toxicologic endpoint was similar for all of the animal species examined and was 650-950 micrograms ml-1, even though the total dose required to cause the toxicologic endpoint varied greatly among the animal species . These findings suggest that the toxicologic effect compartment for respiratory depression is indistinguishable from the plasma compartment, and that species differences in the total dose are due to differences in pharmacokinetics of the drug, mainly in the total body clearance, but not to differences in intrinsic susceptibility to the drug.

Q J Med, 1993 Jul, 86(7), 419 - 24
The risks of symptomatic vaginal candidiasis after oral antibiotic therapy; MacDonald TM et al.; It is generally accepted that antibiotic use can result in vaginal fungal overgrowth, although evidence estimating the extent to which this causes symptomatic vaginitis is scant . In a study using the prescription of vaginal antifungal preparations as a surrogate measure of vaginal candidiasis, a cohort of women taking antibiotics had a higher incidence of vaginal candidiasis after antibiotic exposure than beforehand (relative risk 2.3; 95% confidence interval 1.9-3.0); this risk was highest in those aged 36-40 years (RR 6.0, 95% CI 2.9-12.5) . The attributable risk was highest among those who were taking cephalosporins (AR 12.8%, 95% CI 9.1-16.5) . In a case-control study, comparing previous antibiotic exposure among women using vaginal antifungal agents and matched controls, antibiotic exposure was higher among those using vaginal antifungal agents during the previous 28 days, with an odds ratio of 5.5 (95% CI 3.8-7.9).

Antibiot Khimioter, 1993 Jul, 38(7), 7 - 10
{A novel antibiotic of the aureolic acid group . Isolation, physicochemical and biological properties, identification}; Fedorova GB et al.; An antibiotic complex was extracted from the culture fluid of Streptomyces phaeofaciens, strain 51 . By the physicochemical properties it was referred to the group of aureolic acid . The complex was separated to chromatographically pure components by column chromatography . The main component was designated as antibiotic 51-I . Its physicochemical and biological properties were studied . Comparison of the data on the study of antibiotic 51-I with the respective characteristics of the described antibiotics of the group of aureolic acid suggested that antibiotic 51-I is a new representative of this group.

Antibiot Khimioter, 1993 Jul, 38(7), 37 - 9
{Therapeutic effect of azlocillin and its combinations with other antibiotics in experimental plague infection}; Markovskaia EI et al.; The therapeutic effect of azlocillin and its combinations with other antibiotics was studied in a model of experimental plague of albino mice . Azlocillin was shown to be efficient in the prophylaxis and treatment of the experimental plague infection . The optimal doses of azlocillin were determined . The protective action of the drug depended on the dose and the time of its administration . The therapeutic effect was mainly defined by the antibiotic dose . The use of azlocillin in not sufficiently active doses in combination with aminoglycosides (gentamicin, sisomicin and amikacin), rifampicin or doxycycline significantly increased the percentage of the animal survival by comparison with that after the use of every antibiotic alone . A synergistic effect was observed when azlocillin was used in combination with rifampicin or amikacin.

Neurosurgery, 1993 Jul, 33(1), 44 - 9
Penetration of intravenous antibiotics into brain abscesses; Yamamoto M et al.; INTRA-ABSCESS CONCENTRATIONS OF the intravenously administered latamoxef (LMOX, moxalactam in the United States) and cefotetan (CTT), were studied in 11 patients with intracranial abscess . None of these patients underwent surgical ablation of the abscess . In all cases, the abscess was aspirated, and multiple aspirations were required in five patients . Antibiotic concentrations in 18 aspirates were, therefore, determined by the agar well method . LMOX concentrations in 16 aspirates drawn from nine brain abscess cases ranged from 0 to 10.9 micrograms/ml, with a mean (standard deviation) of 4.18 (3.04) micrograms/ml . The CTT concentration in one patient with a brain abscess was 8.51 micrograms/ml, and the LMOX concentration in the one remaining patient with subdural empyema was 5.20 micrograms/ml . In one patient, the serum-to-pus penetration rate of LMOX was estimated to be 0.11 against the peak value of the concentration in serum or 0.44 against the simultaneously obtained level in serum . Significantly higher concentrations of LMOX were produced in abscess cavities with multiple-dose administration or by prior drainage of pus . More-advanced stages of local inflammation, as demonstrated by computed tomography, correlated with higher concentrations . However, the routine indexes of systemic inflammation, such as body temperature, white blood cell count, and level of C-reactive protein in serum, cannot be used to predict the concentration present in intracerebral pus . A tendency for LMOX concentrations in pus obtained after single dose-administration to decrease with increasing duration from symptom onset to sampling was observed but was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Nat Genet, 1993 Jul, 4(3), 289 - 94
Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness; Prezant TR et al.; Maternally transmitted non-syndromic deafness was described recently both in pedigrees with susceptibility to aminoglycoside ototoxicity and in a large Arab-Israeli pedigree . Because of the known action of aminoglycosides on bacterial ribosomes, we analysed the sequence of the mitochondrial rRNA genes of three unrelated patients with familial aminoglycoside-induced deafness . We also sequenced the complete mitochondrial genome of the Arab-Israeli pedigree . All four families shared a nucleotide 1555 A to G substitution in the 12S rRNA gene, a site implicated in aminoglycoside activity . Our study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non-syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic-induced ototoxicity.

Hosp Pract (Off Ed), 1993 Jul, 28 Suppl 2, 40 - 3; discussion 61-2
Outpatient parenteral antibiotic therapy . Management of serious infections . Part II: Amenable infections and models for delivery . Infusion center, office, and home; Poretz DM; Outpatient parenteral antibiotic therapy (OPAT) administered in an infusion center often offers the advantages but not the expense of the hospital setting . Office-based OPAT maintains the physician-patient relationship but may be impractical for the physician . Home administration is ideal for selected patients, but when it is provided by an infusion company, the physician may be sidestepped.

Science, 1993 Jun 4, 260(5113), 1500 - 3
Footprinting the sites of interaction of antibiotics with catalytic group I intron RNA; von Ahsen U et al.; Aminoglycoside inhibitors of translation have been shown previously to inhibit in vitro self-splicing by group I introns . Chemical probing of the phage T4-derived sunY intron shows that neomycin, streptomycin, and related antibiotics protected the N-7 position of G96, a universally conserved guanine in the binding site for the guanosine cofactor in the splicing reaction . The antibiotics also disrupted structural contacts that have been proposed to bring the 5' cleavage site of the intron into proximity to the catalytic core . In contrast, the strictly competitive inhibitors deoxyguanosine and arginine protected only the N-7 position of G96 . Parallels between these results and previously observed protection of 16S ribosomal RNA by aminoglycosides raise the possibility that group I intron splicing and transfer RNA selection by ribosomes involve similar RNA structural motifs.

Postgrad Med, 1993 Jun, 93(8), 173 - 80
Antibiotics for nursing home residents . When are they appropriate?
Katz PR.
Antibiotics are used often in nursing homes in response to high rates of infection . Physicians and nursing home administrators and staff need to work in concert to avoid inappropriate prescription of antibiotics in this setting . Physicians need to know how infection presents in frail, institutionalized elderly patients; strive to prevent infection; and prescribe antibiotics only in situations in which clear benefit has been demonstrated . Nursing home administrators and staff must institute comprehensive infection control programs, adopt specific guidelines for antibiotic use, and keep physicians informed about the number and types of infections and antibiotic susceptibility patterns.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 6 - 10
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . The team concept; Tice AD; The delivery of outpatient parenteral antibiotic therapy is a team effort that, at minimum, requires a physician, a nurse, and a pharmacist . Other specialists may be added as needed . The team may be structured in several different ways, but two basic models emerge: physician-directed and nonphysician-directed . Whatever the structure, the physician should maintain a leadership role in the care of the patient.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 52 - 7
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Legal issues; Lawton SE; The tremendous growth of outpatient services has spurred closer legal scrutiny of patient referrals to physician-owned companies (self-referral) . Federal "safe harbor" regulations protect certain arrangements, but much of the law remains vague . Future legislation is likely to be more specific, however . Physicians should obtain legal counsel before entering into any ownership or investment opportunities in home infusion therapy.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 44 - 51
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Reimbursement; Tierce JC; Reimbursement for outpatient parenteral antibiotic therapy (OPAT), like that for all health care, is regulated by a multitude of private and public policies . Not all payers reimburse all aspects of OPAT, and with those that do, obtaining payment can be a daunting task . A key to prompt payment is the correct billing code . An overview of office-based, home-based, and hospital-based OPAT reimbursement is presented.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 39 - 43
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Costs and benefits; Milkovich G; The costs of outpatient parenteral antibiotic therapy are outweighed by the benefits to all involved: provider, payer, patient, and society . Simple comparisons of inpatient and outpatient charges are not a true measure of costs . Recent in-depth cost-benefit analyses reveal a significant saving when indirect benefits, such as increased productivity and quality of life, are included . Even so, financial issues remain to be addressed.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 33 - 8
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Quality assurance; Kunkel MJ; At present, there are no accepted guidelines for quality assurance in the outpatient setting, although they are being developed . Greater emphasis is being placed on ongoing rather than retrospective improvement of quality, as measured by the care-giving process and outcome . Thus, programs need to incorporate sound methods for teamwork, communication, and documentation of services.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 28 - 32
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Pediatric considerations; Bradley JS; Outpatient parenteral antibiotic therapy (OPAT) is less threatening to children than in-hospital treatment and most likely reduces the risk of nosocomial infection . Most pediatric infections can be treated in the home if patients are medically stable, parents are motivated to help with therapy, and appropriate resources, such as skilled pediatric nursing, are available . The cost of pediatric OPAT is similar to that of adult OPAT.

Hosp Pract (Off Ed), 1993 Jun, 28 Suppl 1, 21 - 7
Outpatient parenteral antibiotic therapy . Management of serious infections . Part I: Medical, socioeconomic, and legal issues . Advances in i.v . delivery; Kravitz GR; Physicians who prescribe outpatient parenteral antibiotic therapy must remain abreast of advances in intravenous catheters and infusion pumps so they can select equipment that realizes the full potential of therapy and suits the patient's needs for comfort, reliability, and safety . The cost of equipment and installation can vary greatly and is thus another important consideration when choosing these devices.

Clin Orthop, 1993 Jun, (291), 303 - 12
The effects of antibiotic-impregnated autogeneic cancellous bone graft on bone healing; Lindsey RW et al.; Autogeneic cancellous bone graft has been recommended as a vehicle for local antibiotic delivery . Its effect on graft incorporation, however, is unknown . The healing of defects grafted with tobramycin-impregnated cancellous bone were compared with those grafted with cancellous bone alone . Plane roentgenographs, microradiographs, bone density analyses, histologic examination, and biomechanical testing were performed on specimens throughout the course of healing . The presence of large concentrations of local tobramycin does not appear to affect the normal healing characteristics of cancellous bone graft.

Biochemistry, 1993 Jun 1, 32(21), 5548 - 53
Some characteristics of DNA strand scission by macromolecular antitumor antibiotic C-1027 containing a novel enediyne chromophore; Sugiura Y et al.; A new macromolecular antitumor antibiotic, C-1027, shows potent cytotoxic effects and DNA cutting activity . The DNA cleaving properties of C-1027 are compared with those of other enediyne compounds such as neocarzinostatin, esperamicin A1, and calicheamicin gamma 1 . Even in the absence of thiols or reductants, the antibiotic C-1027 has high DNA breakage ability . Of special interest is the fact that C-1027 causes strand breaks two base pairs apart at specific sites such as 5'-TAT/3'-ATA and 5'-AGA/3'-TCT (cleavage sites in italics) in the two strands . This novel double-stranded cleavage fashion is different from that of calicheamicin gamma 1, which is found to have a 3-bp separation between cleavage sites on the two strands . The asymmetric cleavage pattern to the 3'-side and a competitive experiment with distamycin A reveal minor-groove interaction of double-helical DNA with C-1027 . This antibiotic appears to oxidize DNA through hydrogen abstraction predominantly at the C-4' carbon of deoxyribose . The activation mechanism of C-1027, which contains an enediyne chromophore of the esperamicin/calicheamicin type, has been proposed.

J Infect Dis, 1993 Jun, 167(6), 1336 - 43
Effect of antibiotic class and concentration on the release of lipopolysaccharide from Escherichia coli; Evans ME et al.; The ability of six antibiotics from different classes to release radiolabeled lipopolysaccharide (LPS) from a phenotypically smooth galE mutant of Escherichia coli O111:B4 was examined . Antibiotic concentrations were 0.0625-512 micrograms/mL . LPS release increased as a function of the antibiotic concentration, reaching a limit at or near the concentration that killed the majority of bacteria . The maximum amount of LPS released by polymyxin B was 40.6% +/- 0.9%, by gentamicin 58.2% +/- 2.5%, by ciprofloxacin 65.8% +/- 2.5%, by ceftazidime 73.1% +/- 0.9%, by tetracycline 75.3% +/- 10.0%, and by imipenem 79.7% +/- 2.3% . In timed experiments, ceftazidime released 61.9% +/- 1.2%, imipenem 51.1% +/- 8.8%, and tetracycline 39.7% +/- 4.4% of the LPS within the first hour of incubation, whereas polymyxin B released 13.5% +/- 1.9%, gentamicin 9.8% +/- 3.6%, and ciprofloxacin 12.7% +/- 2.6% of the LPS (P < .05) . Fluoro-radiography and immunoblot analyses revealed similar migration patterns for antibiotic-released and cell-bound LPS on SDS-PAGE gels, suggesting similar O-polysaccharide content in the two LPS fractions . The amount and rate of LPS release from an E . coli strain was dependent upon antibiotic class and concentration.

J Neurosurg, 1993 Jun, 78(6), 938 - 43
Epileptogenic effect of antibiotic drugs; Grondahl TO et al.; The epileptogenicity of antibiotic drugs represents a clinical problem, and it is well known that the use of penicillin and certain other preparations can induce seizures . In the present study, the authors investigated the epileptogenic properties of different concentrations of 12 commonly used antibiotic medications belonging to seven separate groups . The drugs were tested in the hippocampus, which has a low threshold for the development of epileptiform activity . The hippocampal slice technique, using rat tissue, was employed since absence of the blood-brain barrier allows administration of the drugs in known concentrations . The preparation was exposed to antibiotics in known concentrations and the amplitude and number of population spikes were recorded . Penicillin G was used as a reference substance . Cloxacillin (> or = 1 gm/liter), cephalothin (> or = 1 gm/liter), gentamicin (> or = 80 mg/liter), chloramphenicol (> or = 1 gm/liter), ciprofloxacin (> or = 50 mg/liter), erythromycin (> or = 1 gm/liter), and ampicillin (> or = 1 gm/liter) showed moderate to marked epileptogenic effects, whereas cefuroxime, clindamycin, cefotaxime, vancomycin, and tobramycin had no epileptogenic effects.

Cesk Farm, 1993 Jun, 42(3), 143 - 4
{Preparation of the first peroral antibiotic, Anginol-tablet}; Novacek L; In 1892-1896 Ivan Honl and Jaroslav Bukovsky successfully tested pyocyaneoprotein (pyocynase), later used as the pharmaceutical preparation Tonsilan, in the therapy of crural ulcers and other bacterial diseases . In 1911 Honl prepared pyocyaneoprotein as the first antibiotic in the form of tablets called Anginol-tablets . Anginol was used in the Czech Lands in infectious diseases of the pharynx and larynx, particularly in tonsillitis, until the end of the Second World War . The present paper reports the procedure of compounding Anginol-tablets and their composition.

Crit Care Nurs Clin North Am, 1993 Jun, 5(2), 313 - 23
Antibiotic agents in critical care; McCraney S et al.; The practice of infectious disease and the use of antibiotics are becoming more and more complex in the critical care patient . Critical care nurses continue to play an important role in the safe administration and the postadministration monitoring of antibiotics . Important issues include the choice of drug for specific infections, the effect of pharmacokinetics, methods for safe administration, and the postadministration monitoring for effectiveness and for adverse effects.

Ann Plast Surg, 1993 Jun, 30(6), 525 - 30
Investigation of a biodegradable, implantable antibiotic delivery system on rate of wound infection; Sasmor MT et al.; Biodel, a bioabsorbable polymer, may be adapted to serve as an antibiotic delivery system for high local concentrations of drugs . In an autocontaminated, irradiated wound model with a high intrinsic infection rate, implanted gentamicin-impregnated Biodel beads prevented wound infections in the submental area of rats.

J Antibiot (Tokyo), 1993 Jun, 46(6), 942 - 51
Respinomycins A1, A2, B, C and D, a novel group of anthracycline antibiotics . II . Physico-chemical properties and structure elucidation; Ubukata M et al.; Respinomycins A1, A2, B, C and D were revealed to be novel anthracycline antibiotics with molecular formulae of C51H72N2O20, C43H58N2O15, C35H43NO14, C36H45NO14 and C51H70N2O22, respectively . Their structures were determined by means of 1H-1H COSY, 13C-1H COSY and HMBC spectra . The structure of the aglycone of respinomycins was unambiguously determined by LSPD experiments and NOESY . The common skeleton of respinomycins is a new type and is distinguished from that of the nogalamycin group.

J Antibiot (Tokyo), 1993 Jun, 46(6), 928 - 35
Verucopeptin, a new antitumor antibiotic active against B16 melanoma . II . Structure determination; Sugawara K et al.; The structure of a new antibiotic verucopeptin has been determined by the spectroscopic analyses and chemical degradation studies . It is a 19-membered cyclodepsipeptide which is structurally related to azinothricin and A83586C.

J Antibiot (Tokyo), 1993 Jun, 46(6), 921 - 7
Verucopeptin, a new antitumor antibiotic active against B16 melanoma . I . Taxonomy, production, isolation, physico-chemical properties and biological activity; Nishiyama Y et al.; A new antitumor antibiotic verucopeptin was isolated from the culture broth of Actinomadura verrucosospora Q886-2 . It should potent cytotoxicity and specific in vivo activity against B16 melanoma . Maximum T/C value (162%) was obtained by Q1D x 1 treatment schedule.

Br J Dermatol, 1993 Jun, 128(6), 619 - 26
Selective generation of CD8+ T-cell clones from the peripheral blood of patients with cutaneous reactions to beta-lactam antibiotics; Hertl M et al.; The presence, phenotype, and functional characteristics of peripheral blood penicillin-specific T lymphocytes in individuals with cutaneous allergic reactions to penicillin were investigated using in vitro long-term culture techniques . Peripheral blood mononuclear cells from two penicillin-allergic patients were stimulated in vitro with penicillin, and T-cell blasts were clonally expanded by limiting dilution . Seven T-cell clones were derived, all of which were CD3+ CD4- CD8+ HLA-DR+, and produced IL-2 and IFN-gamma upon stimulation . T-cell proliferation required the presence of antigen and autologous, but not allogeneic, antigen-presenting cells . In addition to the parent compound, the T-cell clones also developed a proliferative response to penicilloyl, the major metabolite of penicillin . The cloned T-cell lines were found to exhibit marked suppressor activity for Con A mitogenesis . The observed suppressor activity required cell-to-cell contact, as supernatants from these T-cell clones had no comparable inhibitory effect . These findings indicate that there is a predominance of penicillin-specific CD8+ T cells in the peripheral blood of individuals sensitized to beta-lactam antibiotics.

Antimicrob Agents Chemother, 1993 Jun, 37(6), 1377 - 9
Elimination of quinolone antibiotic carryover through use of antibiotic-removal beads; Zabinski RA et al.; To prove the utility of antibiotic-removal beads in separating antibiotics from bacterial samples, Escherichia coli ATCC 25922 was exposed to five separate quinolones before and after each was exposed to antibiotic-removal beads . Plates treated with antibiotic solutions that were exposed to beads demonstrated antibiotic removal, and plates treated with antibiotic solutions that were not exposed to beads demonstrated antibiotic carryover . After exposure to beads, fluoroquinolone concentrations decreased from 5 micrograms/ml to 0.14 micrograms/ml (ciprofloxacin), 0.04 micrograms/ml (temafloxacin), < 0.01 microgram/ml (ofloxacin), < 0.01 microgram/ml (sparfloxacin), and 0.02 micrograms/ml (clinafloxacin) . These data indicate that antibiotic carryover can be successfully circumvented through the use of antibiotic-removal beads.

Zentralbl Bakteriol, 1993 Jun, 279(2), 157 - 66
Metabolism of phosphate-limited cultures of Streptomyces . IV . Protein-phosphorylation of antibiotics-producing cultures; Ozegowski JH et al.; It has been demonstrated that in the cellular proteins of Streptomyces hygroscopicus JA 6599 and Streptomyces noursei JA 3890 b, the producers of the antibiotics turimycin and nourseothricin, respectively, phosphorylated proteins are present . Numbers and concentrations of phosphorylated proteins decreased during the idiophase as characterized by phosphate limitation, antibiotic biosynthesis and phosphatase formation . Phosphoamino acids of serine, threonine and tyrosine were found in the hydrolysates of proteins . Protein tyrosyl kinase was demonstrated in the cellular extracts . The results supports the hypothesis that protein phosphorylation possesses a function in the regulation of growth and secondary product formation.

Antibiot Khimioter, 1993 Jun, 38(6), 8 - 11
{Use of the protoplast fusion and regeneration method for screening antibiotic producers among inactive strains of Streptomyces}; Malanicheva IA et al.; Intraspecies fusion of protoplasts of two strains of Streptomyces fradiae, i.e native protoplasts of an inactive strain INA 00708 and heat inactivated protoplasts of a neomycin-producing strain ATCC 10745, and regeneration of the protoplasts of the inactive strain INA 00708 resulted in formation of clones producing neomycin and clones synthesizing antibiotics of an unknown nature differing from neomycin . All the active clones were unstable and lost their antibiotic activity in subcultures . Regeneration of the protoplasts of 4 different inactive strains of Streptomyces sp . also resulted in formation of active clones which were unstable and lost their capacity for the antibiotic synthesis after the first subculture . The data in principal indicate to the possible use of protoplast fusion and regeneration in screening of cultures producing new antibiotics among inactive strains of streptomycetes . However, the efficiency of such procedures is low since the experiments are labor-consuming and the resulting active clones are genetically unstable.

J R Coll Surg Edinb, 1993 Jun, 38(3), 167 - 9
Audit of antibiotic policy and wound infection in neck surgery; Murdoch DA et al.; Neck surgery on 100 consecutive patients in a unit with an established antibiotic policy was studied . An infection rate of 3% was recorded, comparing well with previously published studies . There were no major sequelae in the infected cases . A policy of no perioperative antibiotics for 'clean' surgery for benign disease, cefuroxime for 'clean' surgery for malignant disease and cefuroxime plus metronidazole for 'clean contaminated' surgery is vindicated.

FEMS Microbiol Lett, 1993 May 15, 109(2-3), 123 - 9
Synchronous germination of Streptomyces antibioticus spores: tool for the analysis of hyphal growth in liquid cultures; Miguelez EM et al.; We have devised a method for obtaining synchronous and dispersed growth of Streptomyces antibioticus in liquid cultures . After ultrasonic treatment, most of the spores germinated at the same time, yielding hyphae very similar in length . Dispersed growth was achieved in media without Ca2+ and in which the levels of Fe2+ and Mg2+ were carefully controlled . Studies on the kinetics of growth carried out with synchronous cultures of young hyphae revealed a multiphasic pattern of hyphal elongation, with successive periods of linear growth and changes in growth rate at defined intervals.

Thromb Haemost, 1993 May 3, 69(5), 503 - 8
Beta-lactam antibiotics inhibit agonist-stimulated platelet calcium influx; Burroughs SF et al.; beta-lactam antibiotics cause platelet dysfunction with reversible agonist-receptor inhibition, irreversible {14C}-penicillin binding, and inhibition of agonist-stimulated elevation in cytosolic Ca2+ ({Ca2+}i), occurring after 24 h exposure in vitro and after in vivo treatment . We investigated beta-lactam antibiotic-induced inhibition of rises in {Ca2+}i stimulated by thrombin, sodium arachidonate or A23187 to determine whether Ca2+ influx or intracellular release was primarily affected . The mean rise in {Ca2+}i, measured with fura-2-AM, was inhibited 43.7-84.1% by penicillin when the extracellular Ca2+ concentration ({Ca2+}e) was 1 mM, but was significantly less inhibited when {Ca2+}e was < 1 microM . NiCl2 (2 mM), that blocks Ca2+ influx, caused inhibition comparable to penicillin . MnCl2 (1 mM), that quenches the intracellular fura-2 signal, significantly decreased the rise in 1 mM {Ca2+}i when {Ca2+}e was 1 mM, but did not increase the inhibition caused by penicillin . Penicillin did not inhibit the rise in {Ca2+}i stimulated by inositol-1,4,5-trisphosphate or GTP gamma S . Therefore, beta-lactam antibiotics inhibit agonist-induced elevations of {Ca2+}i primarily through inhibition of Ca2+ influx, which probably accounts for the irreversible inhibition of platelet function seen after prolonged in vitro or in vivo treatment.

J Antibiot (Tokyo), 1993 May, 46(5), 791 - 802
Conformation studies on and assessment by spectral analysis of the protein-chromophore interaction of the macromolecular antitumor antibiotic C-1027; Otani T; Characterization of the secondary structure of the antitumor antibiotic C-1027 has been made from a comparison of C-1027 and its apoprotein by various analytical means . The results indicated the antibiotic to be abundant in beta-structure by measurements of Fourier-transform infrared (FT-IR) spectroscopy and the circular dichroism (CD) spectrum, and by a prediction of the secondary structure based on the amino acid sequence of the peptide . In comparison of the IR spectra of their proteins in D2O, the apoprotein exhibited a faster H-D exchange than C-1027, indicating an increase in the "non-motile parts" of the beta-sheets formed through the protein-chromophore interaction in holo-C-1027 . The prediction of hydropathic index indicated the hydrophobic residues of the apoprotein to be predominantly located in the beta-sheet structures, suggesting hydrophobic interaction in the binding between chromophore and apoprotein . Further, the interaction between chromophore and apoprotein was detected by a fluorescence method . The result showed the dissociation constant (Kd) to be 6.88 x 10(-5) M, indicating that the chromophore is tightly bound to the protein moiety.

J Bone Joint Surg Am, 1993 May, 75(5), 714 - 20
Antibiotic-leaching from polymethylmethacrylate beads; Seligson D et al.; Aminoglycoside-impregnated polymethylmethacrylate beads, which are used to deliver antibiotic directly to infected sites in the musculoskeletal system, are available as a manufactured product or they can be mold-made by a pharmacy or hand-rolled by the orthopaedist in the operating suite . We investigated the leaching of antibiotic from each of these types of beads . Our hypothesis was that the elutions of antibiotic from the three types of beads are similar . Three study groups (hand-made, mold-made, and manufactured beads), each composed of four five-bead subsets, were formed so that twenty beads of each type were tested . Each bead was leached daily in a two-milliliter aliquot of normal saline solution throughout a sixty-day period, and the aminoglycoside concentration in twenty of these aliquots was determined . Analysis of variance showed no statistically significant differences when the antibiotic elutions within each subset, between the different subsets, and between the three groups were compared . The clinically important finding of this investigation is that the leaching characteristics of the three types of aminoglycoside-impregnated beads are equivalent when the beads have been fabricated out of comparable materials.

Prof Nurse, 1993 May, 8(8), 510 - 2
Be alert to an avoidable problem . Management and prevention of antibiotic-acquired diarrhoea; Robinson B; Antibiotic-associated diarrhoea is an unpleasant and distressing problem for patients and health professionals alike . Although this condition can be treated with drugs, patient relapses are common . Implementation of rigorous infection control policies are therefore required.

J Clin Anesth, 1993 May-Jun, 5(3), 212 - 5
Interaction of antibiotics on pipecuronium-induced neuromuscular blockade; de Gouw NE et al.; STUDY OBJECTIVE: To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug) . DESIGN: Prospective, randomized, placebo-controlled study . SETTING: Inpatient gynecologic and gastroenterologic service at a university medical center . PATIENTS: Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia . INTERVENTIONS: Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen . Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response . At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo . MEASUREMENTS AND MAIN RESULTS: The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist . RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test . Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin . CONCLUSIONS: When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

J Pharm Sci, 1993 May, 82(5), 518 - 20
Extraction and analysis by high-performance liquid chromatography of antibiotics in a drug delivery system for farmed fish; Rogstad A et al.; Simple assays for extraction and determination of the concentrations of the antibiotics oxytetracycline, oxolinic acid, and flumequine in a drug dosage form for farmed fish are described . HPLC with UV detection was used in the analyses . The recovery of all three drugs was approximately 100%, and the precision varied from 0.5-3.0% . The methods are applicable to the production control, quality control, and stability control of the products.

Hear Res, 1993 May, 67(1-2), 13 - 9
Aminoglycoside antibiotics inhibit maxi-K+ channel in single isolated cochlear efferent nerve terminals; Takeuchi S et al.; Patch clamp recordings were obtained from isolated cochlear efferent nerve terminals . The effect of aminoglycoside antibiotics on single maxi-K+ channels was determined . At positive voltages (cytosol with respect to extracellular side), neomycin, streptomycin, and kanamycin significantly reduced the single channel current amplitude of the maxi-K+ channel from the cytosolic side . The IC50 for neomycin was 9.10(-4) M from the cytosolic side and >> 10(-3) M from the extracellular side . Streptomycin and kanamycin were less potent . No significant difference in inhibition of the single channel current amplitude by 2.5.10(-4) M cytosolic neomycin was observed between 7.10(-4) M and 10(-6) M free cytosolic Ca2+ . Neomycin had no significant effect on the open probability of the maxi-K+ channel either from the cytosolic or from the extracellular side . These findings demonstrate that the maxi-K+ channel in cochlear efferent nerve terminals can be a site of action for aminoglycoside antibiotics.

J Antimicrob Chemother, 1993 May, 31 Suppl D, 1 - 16
Pharmacokinetics of antibiotics in natural and experimental superficial compartments in animals and humans; Ryan DM; Transcapillary exchange of antibiotics and other small molecules is diffusion driven and occurs in the capillary beds of the tissues . Small polar molecules are ionized at physiological pH and diffusion is pore-mediated . More lipophilic substances can also leave capillaries by the transcellular route . Splanchnic tissues have fenestrated capillary walls while somatic tissues have mainly micropores in their capillary walls . Under normal physiological conditions the ratio of capillary surface area to volume of fluid present (SA/V) is very large (> 100) and the rate of exchange of substances between capillaries, interstitial fluid and tissue fluid is extremely rapid . The structure of the interstitial space or ground substance, linking the capillary to the tissue cells, is designed to regulate the exchange of water, albumen and other solutes between the plasma and tissues . Interstitial space fluid (tissue fluid) is not simply an ultrafiltrate of plasma and has a specific chemical imbalance with plasma . Some antibiotics bind to serum albumen and it is claimed that this impairs their ability to penetrate into tissue fluids . However, the reduced concentration of albumen in the tissue fluid, relative to the plasma, is the main reason why percentage tissue penetration data based on total levels present are misleading and perpetuate the misconception that highly bound antibiotics (> 80%) have a reduced penetration potential . The majority of infections are localized in extracellular fluid . Several models have been developed to sample serially the extracellular compartment . They have yielded diverse concentration/time profiles even for the same antibiotic at similar sites (skin and subcutaneous tissues) . It has been shown that the various profiles are a direct consequence of compartment SA/V, which can range from > 100 to < 10 . In the preclinical situation, the blister model has proven popular and reproducible but it should be remembered that the delayed profile seen is an artefact of blister geometry (SA/V < 10) . On the evidence available it is likely that bacterial infections, in the presence of acute inflammation, will enhance the rate of entry of agents, while the reverse is true in areas of chronic inflammation where pathological barriers are already in place.

J Antimicrob Chemother, 1993 May, 31(5), 739 - 47
Evaluation of delayed type hypersensitivity to beta-lactam antibiotics in mice; Hattori H et al.; This study was designed to determine whether delayed type hypersensitivity could be evoked by protein-unconjugated beta-lactam antibiotics emulsified with Freund's complete adjuvant (FCA) in mice . The method providing the strongest sensitization was assessed by measuring footpad swelling induced by several biweekly intervals of subcutaneous injections of 0.8 mg/mouse cephalothin with FCA, followed by intradermal challenge with 1.0 mg/site cephalothin into the footpad in four different strains of female mice . A total of three and four injections, once every two weeks, in BDF1 and DBA/2 mice, respectively, produced the greatest potential for swelling . This swelling could be reinduced by the local passive transfer of cephalothin-primed splenocytes into the footpad of naive recipient mice . Moreover, the reaction was diminished by the addition of anti-Thy-1.2 monoclonal antibody with low-toxicity rabbit complement to cephalothin-primed splenocytes . Swelling in the footpad was therefore induced via the delayed type hypersensitivity reaction, indicating T-lymphocyte dependence . When the potential for beta-lactam antibiotics to elicit delayed type hypersensitivity was investigated in BDF1 mice, eight of the nine agents employed showed a 10-90% positive incidence . This result had a significant correlation (r = 0.76) with the data for skin reaction in guinea pigs, the method generally used for estimating allergenicity . These results suggest that this procedure may be a useful tool for evaluating delayed type hypersensitivity induction during the early development of novel antibiotics, since not only can sensitization be induced with protein-unconjugated antibiotic, but also because assessment can be made using a small amount of sample.

Mol Microbiol, 1993 May, 8(3), 571 - 82
Streptomyces antibioticus contains at least three oleandomycin-resistance determinants, one of which shows similarity with proteins of the ABC-transporter superfamily; Rodriguez AM et al.; Three different DNA fragments of an oleandomycin producer, Streptomyces antibioticus, conferring oleandomycin resistance were cloned in plasmid pIJ702 and expressed in Streptomyces lividans and in Streptomyces albus . These oleandomycin resistance determinants were designated as oleA (pOR400), oleB (pOR501) and oleC (pOR800) . oleA and oleC are closely linked in the chromosome as they were both obtained together in two cosmid clones that were isolated from a genomic library . Sequencing of the oleC resistance determinant revealed four complete open reading frames (ORFs) and the C-terminal end of a fifth . The functions of orf1 and orf2 are unknown since they did not show significant similarity with other sequences in the data bases . The orf3 gene product has similarity with some proteins involved in iron and vitamin B12 uptake in bacteria . The orf4 gene product had a hydrophilic profile and showed important similarity with proteins containing typical ATP-binding domains characteristic of the ABC-transporter superfamily and involved in membrane transport and, particularly, with several genes conferring resistance to various macrolide antibiotics and anticancer drugs . The last gene, orf5, is translationally coupled to orf4 and codes for a hydrophobic polypeptide containing several transmembrane domains characteristic of integral membrane proteins . Subcloning and deletion experiments limited the resistance determinant to a 0.9 kb PstI-SphI fragment and only orf4 is included in this fragment . These results suggest that resistance to oleandomycin conferred by oleC (orf4) is probably due to an efflux transport system of the ABC-transporter superfamily.

J Pharm Pharmacol, 1993 May, 45(5), 466 - 72
Evaluation of the inhibitory activity on serine and aspartic proteases of 4-amino-4H-1,2,4-triazole and 5-aminothiazole derivatives structurally related to beta-lactam antibiotics; Vilain AC et al.; Twenty new derivatives of 4-amino-4H-1,2,4-triazole and 5-aminothiazole have been examined for their inhibitory potential towards serine and aspartic proteases . Upon prolonged incubation with enzyme, the phenylacetylaminothiazolium salts exhibit progressive, time-dependent inhibition of chymotrypsin according to a first-order process . The formation of a tetrahedral transition state-like complex by attack of the active-site serine at the C2-position of the pseudobase form of the thiazolium may be responsible for the observed effect . Triazolium salts appeared to be simple competitive inhibitors of this enzyme, effective in the mM range concentration . Poor inhibitions of trypsin and pepsin were also obtained in the triazolium series . In spite of their structural analogy with beta-lactams, the selected derivatives failed to inhibit human leucocyte elastase.

Clin Exp Immunol, 1993 May, 92(2), 218 - 24
Therapeutic effect of granulocyte colony-stimulating factor and cephem antibiotics against experimental infections in neutropenic mice induced by cyclophosphamide; Wakiyama H et al.; Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) against severe infections in cyclophosphamide (CY)-induced neutropenic mice were investigated by its single use or by its combination with cephem antibiotics . Treatment with rhG-CSF increased the number of peripheral blood leucocytes and strikingly shortened the duration of the neutropenic state . Most of the regained population in the peripheral blood leucocytes were neutrophils . Functions of neutrophils, such as phagocytic activity, superoxide release, and expression of Mac-1 molecules, were remarkably enhanced by administration of rhG-CSF . When rhG-CSF was administered to CY-induced neutropenic mice before infection, protective effects against various kinds of bacteria were remarkable . On the other hand, such remarkable effects were not observed when rhG-CSF was administered after infections . However, even in the case of post-infectious treatment, a combination therapy of rhG-CSF with cephem antibiotics, particularly with Cefodizime (CDZM), showed a significant improvement in the survival rate and a decrease in the number of viable bacteria in the liver . These results suggest that a combination therapy of rhG-CSF with cephem antibiotics, especially with CDZM, is an efficient regime against severe infections in patients with neutropenia induced by a heavy anti-tumour chemotherapy.

Am J Ophthalmol, 1993 Apr 15, 115(4), 471 - 7
Comparison of topical ciprofloxacin to conventional antibiotic therapy in the treatment of ulcerative keratitis; Parks DJ et al.; We evaluated the efficacy of ciprofloxacin (3 mg/ml) as the sole topical antibiotic used to treat infectious keratitis in 14 patients . We compared the ciprofloxacin-treated group to a retrospective control group of 30 consecutive culture-positive patients treated with conventional therapy in which cefazolin (50 mg/ml) and fortified gentamicin sulfate (9.1 mg/ml) solutions were used . We found no remarkable difference between the control group and the ciprofloxacin-treated group regarding patient age, risk factors, need for hospitalization, and virulence of organism isolated . The average time to healing in culture-positive ciprofloxacin-treated patients was 34 +/- 33 days vs 45 +/- 71 days in the control group and this difference was not statistically significant . The duration of antibiotic therapy in the culture-positive ciprofloxacin-treated group was 27 +/- 15 days vs 33 +/- 50 days in the control group . Four of the 30 control patients required modification of their antibiotic regimen, whereas no ciprofloxacin-treated patient required a change . Ciprofloxacin appears to be an effective single agent in the treatment of ulcerative keratitis.

J Biol Chem, 1993 Apr 5, 268(10), 6831 - 4
Combined purification of actinomycin synthetase I and 3-hydroxyanthranilic acid 4-methyltransferase from Streptomyces antibioticus; Jones GH; Actinomycin synthetase I, which activates the precursor of the chromophore of actinomycin, has been purified nearly 1000-fold from extracts of Streptomyces antibioticus . The enzyme has an M(r) of 45,000 and appears to function as a single polypeptide chain . The formation of the enzyme is repressed when S . antibioticus mycelium is grown on glucose as a carbon source . Several benzoic acid derivatives, including intermediates in the putative pathway for actinomycin biosynthesis, were capable of supporting ATP-pyrophosphate exchange catalyzed by actinomycin synthetase I . Interestingly, three synthetic phenoxaziones also functioned as substrates in the exchange reaction . It proved possible to purify a second enzyme involved in actinomycin biosynthesis, 3-hydroxyanthranilic acid 4-methyltransferase, from the same extracts prepared for the purification of actinomycin synthetase I and by similar procedures . Streptomyces lividans, previously shown to contain a silent gene for the enzyme phenoxazione synthase, apparently does not contain a silent pathway for the complete synthesis of actinomycin since neither actinomycin synthetase I nor the methyltransferase could be detected in strains containing a cloned sequence that activates phenoxazione synthase expression.

Ulster Med J, 1993 Apr, 62(1), 50 - 7
Antibiotic pharmacoeconomics: an attempt to find the real cost of hospital antibiotic prescribing; Kerr JR et al.; Antibiotics account for a large part of all hospital pharmacy budgets, but the actual cost of their prescription is unknown . These costs include intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices, disposal of sharps and adverse effects . An in-house method of costing antibiotic therapy is presented, to quantify these hidden expenses . Since not only an awareness, but an accurate quantification, of hidden costs is required, a study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward; this involved the identification of particular staff members performing various procedures, consumables used and time taken . The cost of five-day courses of gentamicin, penicillin G, ampicillin, flucloxacillin, cefuroxime, ceftotaxime and erythromycin has been calculated; drug and hidden costs for each are presented graphically for comparison . The breakdown cost for gentamicin is presented to illustrate the method . The costing of adverse effects has not been attempted . We suggest that costings of this sort are used in cost-benefit analysis of antibiotic use . These calculations have been incorporated into a computer spreadsheet and this costing service will be offered to clinical areas of our hospital.

J Antibiot (Tokyo), 1993 Apr, 46(4), 598 - 605
Pradimicins T1 and T2, new antifungal antibiotics produced by an actinomycete . II . Structures and biosynthesis; Hasegawa T et al.; Pradimicins T1 and T2 are new members of the pradimicin family of antibiotics produced by an actinomycete strain AA3798 . Pradimicins T1 and T2 are dihydrobenzo{a}naphthacenequinones substituted with 3 and 2 sugar moieties, respectively . The salient feature in their structures is an L-xylose attached to the phenolic hydroxyl group at C-11 . Bioconversion experiments using a blocked mutant B-54 of strain AA3798 not only explored a plausible biosynthetic pathway of pradimicins T1 and T2, but also provided evidence of 5S,6S configuration.

Int J Syst Bacteriol, 1993 Apr, 43(2), 297 - 301
Kibdelosporangium albatum sp . nov., producer of the antiviral antibiotics cycloviracins; Tomita K et al.; A new species of the genus Kibdelosporangium is described . This soil organism forms long straight spore chains and numerous sporangium-like structures on the aerial mycelium . The new species has type IV cell walls and pattern A whole-cell sugars (meso-diaminopimelic acid, arabinose, and galactose are present), type PII phospholipids, MK-9(H4) as the major menaquinone, and no mycolic acids . On the basis of morphology and chemotaxonomy, the single isolate is assigned to the genus Kibdelosporangium . The isolate differs from two previously described species of the genus in fatty acid composition, the absence of melanin formation, and many physiological and biochemical characteristics and is identified as a new species . Accordingly, the name Kibdelosporangium albatum sp . nov . is proposed for this isolate . The type strain is R761-7 (= ATCC 55061).

Gut, 1993 Apr, 34(4), 466 - 9
Short and long term outcome of Helicobacter pylori positive resistant duodenal ulcers treated with colloidal bismuth subcitrate plus antibiotics or sucralfate alone; Bianchi Porro G et al.; Thirty two patients with Helicobacter pylori positive duodenal ulcers resistant to treatment were randomly assigned to 4 weeks' treatment with sucralphate 4 g/day or colloidal bismuth subcitrate 480 mg/day plus amoxycillin from days 1 to 7 and tinidazole from days 8 to 14 . After 4 weeks, patients with unhealed ulcers were crossed over to the other form of treatment for a further 4 week period . Patients with healed ulcers were followed up for 1 year without maintenance therapy with clinical and endoscopic investigations 3, 6, and 12 months after healing . Complete healing rates at 4 weeks were 88% (15 of 17) in the colloidal bismuth subcitrate plus antibiotics group and 40% (six of 15) in the sucralphate group (p < 0.05) . After cross over, overall healing rates were 88% (22 of 25) and 47% (eight of 17), respectively (p < 0.05) . H pylori eradication occurred in 83% of patients treated with the triple therapy . Cumulative relapse rates at 12 months were 12% (two of 17) in patients in whom H pylori had been eradicated and 100% (10 of 10) in those with persistent infection after short term therapy (p < 0.05) . These results show that a colloidal bismuth subcitrate plus antibiotics regimen is highly effective in the short term treatment of resistant duodenal ulcers and that H pylori eradication can change the natural tendency to early recurrence of these ulcers.

Am J Obstet Gynecol, 1993 Apr, 168(4), 1239 - 46
Antibiotics in the treatment of preterm labor; Kirschbaum T; OBJECTIVE: Clinical evidence for a relationship between chorioamnionitis and the onset of preterm labor, supported by well developed biochemical models of that interaction, motivated a review of prospective, randomized trials of antibiotic use in its prevention . STUDY DESIGN: A literature search was made of antibiotic trials applied to women at risk for preterm labor and with a clinical diagnosis of preterm labor after premature preterm rupture of membranes . A review of two retrospective case-control studies conducted on pregnant women with positive cultures for Chlamydia trachomatis is also included . RESULTS AND CONCLUSION: Results of antibiotic use in women with preterm premature rupture of membranes supports significant prolongation of the interval from rupture of membranes to delivery and improvement and neonatal outcome in treated patients.

J Clin Periodontol, 1993 Apr, 20(4), 299 - 303
Prevention of transmission of resistant bacteria between periodontal sites during subgingival application of antibiotics; Preus HR et al.; This study was designed to investigate whether antibiotic resistant micro-organisms are able to contaminate and survive on syringe tips used for subgingival deposition of antibiotics, and to test simple and effective means of disinfecting the syringe tip between applications . In the first part of the study, syringe tips used for application of Minocycline subgingival formula in 20 adult periodontitis patients were cultured for bacteria resistant to this drug before and after disinfecting them with ethanol . The results showed that 80% of the unwashed syringes were culture positive for minocycline resistant bacteria, whereas only 1 ethanol washed syringe tip was contaminated . In part II of the study, after dispensing minocycline periodontal formula in 20 patients, 10 of the syringe tips were washed with ethanol while 10 were left untreated . All syringes were stored in a refrigerator for 8 days, whereafter the tips were sampled for resistant bacteria . 20% of the unwashed tips were contaminated after 8 days incubation at 4 degrees C . None of the ethanol washed syringe tips were culture positive . We conclude that syringe tips may be contaminated with antibiotic resistant bacteria after dispensing the antibiotic in periodontal pockets . The transmission of these bacteria to other periodontal sites may be avoided by disinfecting the syringe tip with ethanol between applications . We have also shown that antibiotic resistant bacteria may survive on the syringe tip following 8 days storage in a refrigerator, suggesting that syringes used for subgingival deposition of an antibiotic should not be stored for reuse.

Vet Hum Toxicol, 1993 Apr, 35(2), 151 - 8
A review of the toxicology of the antibiotic MICOTIL 300; Jordan WH et al.; MICOTIL 300 is a new macrolide antibiotic for the treatment of Bovine Respiratory Disease complex . As with other macrolides used in human and veterinary medicine, overdoses of MICOTIL do not produce pathognomonic lesions . The toxicity dose response varies among laboratory animal and domestic livestock species . However, clinical evidence of MICOTIL toxicity due to large doses is generally a manifestation of the positive chronotropic and negative inotropic cardiovascular effects . No adverse environmental effects are expected from the use of MICOTIL in cattle.

J Am Acad Dermatol, 1993 Apr, 28(4), 595 - 602
Long-term oral antibiotics for acne: is laboratory monitoring necessary?
Driscoll MS, Rothe MJ, Abrahamian L, Grant-Kels JM.
BACKGROUND: The role of laboratory monitoring in patients receiving long-term oral antibiotics for acne vulgaris has not been clearly defined . OBJECTIVE: The purpose of our study was (1) to evaluate the literature for objective evidence on the value of routine laboratory monitoring of the asymptomatic patient receiving oral antibiotics for acne and (2) to determine the utilization of laboratory monitoring of these patients by Connecticut dermatologists . METHODS: We surveyed Connecticut dermatologists by phone and inquired about the laboratory monitoring performed in patients receiving long-term oral tetracycline, minocycline, or erythromycin for acne . RESULTS: Eight published studies reported a total of 777 patients who had laboratory monitoring at various frequencies while receiving oral antibiotics for acne . Only one adverse drug reaction (ADR) was detected in a patient in whom mild hyperbilirubinemia developed . Of the 75 Connecticut dermatologists who participated in our survey, 48 (64%) perform some laboratory monitoring; 29% do so routinely, and 35% under special circumstances . CONCLUSION: Our literature review does not support routine laboratory monitoring in all patients who receive long-term oral antibiotics for acne; rarely does such screening detect an ADR and thus does not justify the cost of such testing . A relatively small proportion of Connecticut dermatologists check laboratory tests more frequently than appears necessary; in our opinion, laboratory monitoring should be limited to patients who may be at higher risk for an ADR.

Arzneimittelforschung, 1993 Apr, 43(4), 484 - 6
Uptake and subcellular distribution of azithromycin in human phagocytic cells . Demonstration of the antibiotic in neutrophil polymorphonuclear leucocytes and monocytes by autoradiography and electron microscopy; Wildfeuer A et al.; Azithromycin (CAS 83905-01-5), a new azalide antibiotic, reached high concentrations in alveolar macrophages obtained from patients . Uptake of {14C} azithromycin by macrophages resulted in an intracellular/extracellular concentration ratio of approximately 634 after 90 min incubation . Electron microscopic autoradiography provided visual evidence for the marked uptake and localization of {3H} azithromycin in human neutrophils and monocytes isolated from healthy volunteers . Quantitative analysis of the autoradiographs showed the distribution of azithromycin over the various compartments of the phagocytic cells.

J Pharmacol Toxicol Methods, 1993 Apr, 29(2), 93 - 8
Pharmacokinetic measurement of drugs in lung epithelial lining fluid by microdialysis: aminoglycoside antibiotics in rat bronchi; Eisenberg EJ et al.; A novel technique for in vivo intrabronchial pharmacokinetic measurements using microdialysis is described . The technique was applied to the measurement of tobramycin and gentamicin in the anesthetized rat . The concentration versus time profiles of the drugs in the lung epithelial lining fluid (ELF) following intravenous bolus administration were determined . The mean penetration ratios into the ELF were determined and found to be 0.36 +/- 0.06 (mean +/- SEM, n = 5) for gentamicin and 0.56 +/- 0.09 (mean +/- SEM, n = 5) for tobramycin . The findings suggest that the technique can be used for intrabronchial pharmacokinetic measurement of drugs in the lung, either as an extension of the bronchoalveolar lavage technique or as a practical alternative to it.

Pathol Biol (Paris), 1993 Apr, 41(4), 289 - 93
{Multicenter study of the in vitro sensitivity of genital mycoplasmas to antibiotics}; Bebear C et al.; The in vitro susceptibility of Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) was evaluated in a multicentric study performed in seven hospitals from different geographic areas in France . During a three month period, 324 Uu and 72 Mh clinical isolates were tested using a system ready for use, SIR Mycoplasma (Sanofi Diagnostics Pasteur) . For Uu, the percentage of strains intermediate (I) or resistant (R) was as follows: doxycycline (3), minocycline (2.5), lymecycline (6.7), erythromycin (72, most I), josamycin (0.9), clindamycin (88), pristinamycin (0.3), ofloxacin (34, most I) . For Mh, the percentage of strains I or R was respectively: doxycycline (2.7), minocycline (5.5), lymecycline (15.2), erythromycin (100), clindamycin (1.4), ofloxacin (2.7), josamycin (0) and pristinamycin (0) . Comparable results were observed in the different geographic areas . The frequency of acquired resistances does not justify modifications in the usual treatment of genital mycoplasma infections but leads to monitor their susceptibility to antibiotics.

Antibiot Khimioter, 1993 Apr-May, 38(4-5), 29 - 32
{Interaction of antibiotics with leukocytes in children of various age groups}; Guliaev AE et al.; The indices of binding of 21 currently used antibiotics to human peripheral leukocytes (the ratio of the cellular and extracellular concentrations) were determined experimentally in regard to various age periods, i.e . at the birth, from 1 to 3 years and from 5 to 9 years of the age . It was shown that during the period up to 5 years of the age the binding lowered, especially to the polymorphonuclear leukocytes and not so much to the lymphocytes . The different parameters of the cell pharmacokinetics in children should be taken into account in chemotherapy of bacterial infections with intracellular localization of the pathogen.

Jpn J Antibiot, 1993 Mar, 46(3), 242 - 50
Effects of 3 aminoglycoside antibiotics (kanamycin, gentamicin and fradiomycin) on the thrombin-induced aggregation and intracellular Ca2+ mobilization of human platelets; Tanihata S et al.; This study was aimed at determining whether the thrombin (TRB)-induced aggregation and intracellular free Ca2+ ({Ca(2+)}i) mobilization of fura-2-loaded human platelets would be affected by aminoglycoside antibiotics (AGs), i.e., kanamycin (KM), gentamicin (GM) and fradiomycin (FRM) with 4, 5 and 6 amino groups in their molecules, respectively . We used pH-adjusted solution of AGs, since the TRB-induced aggregation and {Ca(2+)}i mobilization are pH-dependent . TRB (0.1 U/ml) induced aggregation in the presence of 1 mM external Ca2+ but did not in the absence of external Ca2+ . The 3 AGs reduced the TRB-induced aggregation and the antiaggregating potencies were in the order FRM = GM > KM . TRB-induced {Ca(2+)}i elevation in the presence of external Ca2+ was 3 times higher than in the absence of external Ca2+ and the 3 AGs concentration-dependently reduced the TRB-induced {Ca(2+)}i elevation in the absence of external Ca2+ as well as in its presence, and the potency order was FRM > GM > KM . The IC50 of GM or KM was higher in the absence of external Ca2+ than in its presence, while the IC50 of FRM was scarcely affected by the deprivation of external Ca2+ . These results suggest that the reducing potency of the 3 AGs in the TRB-induced aggregation and {Ca(2+)}i mobilization of human platelets is based on the number of amino groups . Furthermore, it is suggested that GM and KM predominantly reduce the Ca2+ influx rather than the intracellular Ca2+ release but FRM is equieffective in decreasing both of them.

J Laryngol Otol, 1993 Mar, 107(3), 188 - 9
The use of antibiotic/steroid ear drops to reduce post-operative otorrhoea and blockage of ventilation tubes . A prospective study; Salam MA et al.; This prospective randomized study investigates whether the use of antibiotic/steroid ear drops (Betnesol-N) is effective in reducing early post-operative otorrhoea and blockage of ventilation tubes (VTs) . The study included 162 children who had bilateral VT insertion and used Betnesol-N ear drops in one ear only for three days after surgery, the other ear was left as control . These children were reviewed two weeks later and their ears were examined for VT patency, presence of blood or of mucopus . Statistical analysis of our results showed that the use of Betnesol-N ear drops has significantly reduced the incidence of post-operative otorrhoea within two weeks of VTs insertion (p < 0.01) . However, these drops did not have a significant effect on the blockage rates of VTs with dried blood (p > 0.05).

J Antimicrob Chemother, 1993 Mar, 31(3), 373 - 84
The release of endotoxin from antibiotic-treated Escherichia coli and the production of tumour necrosis factor by human monocytes; Dofferhoff AS et al.; The influence of antibiotic-induced release of endotoxin from in-vitro grown Escherichia coli on the production of tumour necrosis factor-alpha (TNF) by human monocytes was studied . Antibiotics tested were: cefuroxime (7.5 and 75 mg/L); ceftazidime (10 and 100 mg/L); aztreonam (10 and 100 mg/L); imipenem (10 and 100 mg/L); and tobramycin (8 mg/L) . The effect of the combination of cefuroxime plus tobramycin, and the effect of taurolidine, an endotoxin-binding agent, on TNF production was also tested . After incubation for 4 h, all antibiotic-treated cultures (high-dose) induced a similar rise in extracellular TNF production when compared to the controls . However, after incubation for 24 h, a significant rise in TNF production was noticed in the cefuroxime and aztreonam-treated cultures (6440 and 5969 ng/L, respectively) compared to the ceftazidime and imipenem-treated cultures (846 and 381 ng/L, respectively) . The cefuroxime-induced release of TNF could be reduced by addition of tobramycin (from 6440 to 1615 ng/L) . Similar differences in TNF production were noticed in cell-associated TNF . Dose-response curves did not demonstrate differences in TNF production in aztreonam or imipenem-treated cultures . However, for both cefuroxime and ceftazidime-treated cultures, low-dose treatment resulted in significantly higher production of TNF . The differences in TNF production between these antibiotics could be explained by the production of filaments following treatment with cefuroxime, aztreonam and low-dose ceftazidime, resulting in late bacterial lysis with high levels of endotoxin, whereas treatment with imipenem or high-dose ceftazidime resulted in the formation of spheroplasts, resulting in early lysis of the bacteria and much lower levels of endotoxin . The addition of taurolidine to either imipenem or aztreonam-treated cultures prevented a rise in TNF production as a result of nearly complete neutralization of the released endotoxin . It was concluded that the observed differences in TNF production by human monocytes in vitro were related to differences in the mechanisms and amount of antibiotic-induced release of endotoxin.

Analyst, 1993 Mar, 118(3), 281 - 7
Agarose gel electrophoresis system for the separation of antibiotics used in animal agriculture; Salvatore MJ et al.; A novel electrophoresis system using agarose gel has been developed for the separation and as an aid in the classification of antibiotics . This system utilizes Nunc cell factory disposable tissue culture dishes, which serve as bioassay dish and cooling chamber for agarose gel, in a custom designed electrophoresis unit . Tris(hydroxymethyl) methylamine-succinate buffer at pH 6.0 and 8.0 are employed as the electrolyte for electrophoresis . Bioautography was used as the indicator of mobility . Any agar diffusion assay can be modified to use this system . A suggested name for this system is Nunc cell factory agarose gel electrophoresis (NUAGE) . Selected antibiotics, representative of the aminoglycoside, beta-lactam, macrolide, moenocinol, peptide, polyene, polyether, quinone and tetracycline classes, were separated with this system.

J Antibiot (Tokyo), 1993 Mar, 46(3), 465 - 77
Studies on the mode of antifungal action of pradimicin antibiotics . III . Spectrophotometric sequence analysis of the ternary complex formation of BMY-28864 with D-mannopyranoside and calcium; Ueki T et al.; Sequence of reactions in the process of ternary complex formation of BMY-28864 with D-mannopyranoside and calcium was spectrophotometrically determined under more strict analytical conditions using metal-free preparations of sugars and the pradimicin derivative at a bandpass slit width of 1 nm . In the first phase of ternary complex formation, BMY-28864 stereospecifically recognized and bound to D-mannopyranoside in the absence of calcium, which was revealed by a visible absorption maximum shift of ca . 8 nm . Subsequently, the BMY-28864-D-mannopyranoside conjugate reacted with calcium to yield the ternary complex, which was detected by an additional visible absorption maximum shift of ca . 8 nm . When the three components were mixed at the same time, both phases simultaneously occurred to produce the ternary complex which was accompanied by a visible absorption maximum shift of 16 nm in total . Based on this two-phased reaction sequence, the mechanism of ternary complex formation of BMY-28864 with D-mannopyranoside and calcium was reexamined in details . Terminal D-mannopyranoside was confirmed to be essential as BMY-28864-specific sugar receptor by in vitro analysis and animal cell experiments . While calcium, strontium and cadmium behaved similar in the in vitro ternary complex formation, the yeast and animal cell experiments showed that only calcium played a dual role as a base in the ternary complex formation and as an effector in physiological disturbances leading to cell death.

J Antibiot (Tokyo), 1993 Mar, 46(3), 455 - 64
Studies on the mode of antifungal action of pradimicin antibiotics . II . D-mannopyranoside-binding site and calcium-binding site; Ueki T et al.; Based on the structure-activity relationship data of BMY-28864 and related pradimicin derivatives, the calcium salt-forming ability and the D-mannopyranoside-specific visible absorption maximum shift of BMY-28864 were analysed in the ternary complex formation of BMY-28864 with D-mannopyranoside and calcium . The free C-18 carboxyl group of BMY-28864 was proved to be the sole site for binding to calcium, while no hydroxyl groups of the aglycone were involved in calcium salt formation . The stereospecific D-mannopyranoside-recognizing ability of BMY-28864 was completely abolished by removal of the C-5 disaccharide moiety, and, more particularly, of the C-5 thomosamine moiety . Close relationship of these findings with the antifungal action was also supported by the in vitro antifungal assay and the potassium leakage induction test.

J Antibiot (Tokyo), 1993 Mar, 46(3), 430 - 40
Biosynthesis of the pradimicin family of antibiotics . III . Biosynthetic pathway of both pradimicins and benanomicins; Kakinuma S et al.; The biosynthetic pathway of the pradimicin-benanomicin family of antibiotics was investigated by using sinefungin and blocked mutants derived from Actinomadura verrucosospora subsp . neohibisca E-40 (a high pradimicin producer) or Actinomadura sp . AB1236 (a benanomicin producer) . Addition of sinefungin to strain E-40, pradimicin A aglycone-producing mutant or strain AB1236 inhibited the formation of 11-O-demethyl-7-methoxypradinone II (11dM-7M-PN II), resulting in the accumulation of 11-O-demethylpradimicinone II and pradimicinone II . By feeding pradimicin A aglycone and its analogs to mutants blocked early in pradimicin or benanomicin biosynthesis, the following results were obtained: 11-O-demethylpradinone II, 11dM-7M-PN II 11-O-demethylpradinone I, 11-O-demethylpradimicinone I and pradimicinone I were converted to pradimicin A or benanomicin A; the remaining 6 aglycone analogs were not incorporated into the antibiotics . Pradimicin B, dexylosylpradimicin C and dexylosylbenanomicin A were converted to pradimicin A, pradimicin C and benanomicin A, respectively . A biosynthetic pathway for the antibiotics is proposed.

J Gen Microbiol, 1993 Mar, 139 ( Pt 3), 591 - 9
Characterization of two different types of resistance genes among producers of fortimicin-group antibiotics; Ohta T et al.; Fortimicin-A (FTM-A; astromicin)-resistance genes (fmr genes) isolated from six producers of the FTM-group of antibiotics were analysed . These genes could be classified into two types by the resistance profiles to aminoglycoside antibiotics and by their DNA homologies . Three genes, fmrT from the istamycin producer Streptomyces tenjimariensis ATCC 31603, fmrS from the sannamycin producer Streptomyces sannanensis IFO 14239 and fmrH from the sporaricin producer Saccharopolyspora hirsuta ATCC 20501, conferred resistance to FTM-A, kanamycin (Km) and neomycin B (Nm-B), but not to gentamicin (Gm) . The other three genes, fmrO from the FTM-A producer Micromonospora olivasterospora ATCC 21819, fmrM from the antibiotic SF-2052 producer Micromonospora sp . SF-2098 (ATCC 31580) and fmrD from the dactimicin producer Dactylosporangium matsuzakiense ATCC 31570, conferred resistance to FTM-A, Km and Gm, but not to Nm-B . No DNA homology was detected between the two types of the resistance genes in Southern-blot analysis . The present results revealed that, in spite of the similarity of their biosynthesis genes, there are at least two different types of resistance genes among the FTM-group antibiotic producers.

Br J Dermatol, 1993 Mar, 128(3), 285 - 95
Clinical and laboratory studies of the photosensitizing potential of norfloxacin, a 4-quinolone broad-spectrum antibiotic; Ferguson J et al.; Cutaneous photosensitivity reactions are a consistent although uncommon feature of the fluoroquinolone group of antibiotics, which are related to nalidixic acid . Objective laboratory and clinical data are now routinely required by regulatory bodies for new drugs suspected of being photosensitizers, but no clear recommendations exist . A series of in vitro tests ranging in complexity revealed a UVA-dependent phototoxic potential for the fluoroquinolone norfloxacin similar to that for ciprofloxacin, and less than that of nalidixic acid . Controlled monochromator phototesting, designed to reveal the clinical characteristics, wavelength dependence and severity of cutaneous reactions in normal subjects showed both norfloxacin and ciprofloxacin to have a weak phototoxic potential which clears within 4 weeks of stopping the drug . UVA wavelengths (335 +/- 30 nm; 365 +/- 30 nm) appear most responsible for producing an asymptomatic erythema which is maximal at 24 h . The clinical study differs from those used previously in being blind, containing positive and negative controls, and phototesting after cessation of drug intake . The methodology has the anticipated limitation of failing to detect idiosyncratic photosensitivity responses.

Int J Clin Pharmacol Ther Toxicol, 1993 Mar, 31(3), 148 - 52
Flomoxef, a new oxacephem antibiotic, does not cause hemostatic defects; Cazzola M et al.; Antibiotics of the beta-lactam class may cause coagulation defects and bleeding . It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity . Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has {1-(2-hydroxethyl)-1H-tetrazol-5-yl} thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain . The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers . Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study . Each patient received ten 1 g i.m . injections of flomoxef at 12-hourly intervals . Apparently, the treatment with this oxacephem antibiotic had no significant effect . PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted . The trend was similar both in men and women . Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1993 Mar, 31(3), 734 - 5
Effectiveness of resins in removing antibiotics from blood cultures; Crepin O et al.; The present study evaluates the effectiveness of BACTEC NR-26A resin-containing medium in removing eight antibiotics from blood cultures . Peak concentrations achievable clinically were chosen . All antibiotics were prepared in fresh human blood samples . Blood samples were obtained prior to and at 15 min and 2, 24, 48, and 72 h after inoculation . Aztreonam, ceftriaxone, imipenem, teicoplanin, and ticarcillin were partially removed from blood cultures.

Am J Med, 1993 Mar, 94(3), 251 - 6
Beta-Lactam antibiotic-induced leukopenia in severe hepatic dysfunction: risk factors and implications for dosing in patients with liver disease; Singh N et al.; PURPOSE: To determine if an association could be established for leukopenia and administration of beta-lactam antibiotic therapy in patients with hepatic dysfunction . If such an association could be found, to determine the incidence, timing, and risk factors for beta-lactam antibiotic-induced leukopenia . PATIENTS AND METHODS: Patients with hepatic dysfunction, i.e., liver transplant recipients as well as patients with end-stage liver disease awaiting liver transplantation, seen at our institution between October 1989 and October 1991, who received 7 or more days of antibiotics, were studied in a prospective observational fashion . Complete blood count was determined at baseline and followed until the completion of the antibiotic course or until the resolution of leukopenia in leukopenic patients . RESULTS: Leukopenia occurred after a mean of 6 days with 23% of the beta-lactam antibiotic courses as compared with 0% with the non-beta-lactam antibiotic courses (p = 0.046) . Development of leukopenia correlated with the severity of liver disease . Patients developing leukopenia had worse synthetic hepatic function as evidenced by a lower serum albumin level (p < 0.01), a lower serum cholesterol level (p < 0.05), and a higher prothrombin time (p < 0.01) as compared with the patients without leukopenia . Leukopenic patients had a lower baseline white blood cell count (p < 0.051) and a lower baseline platelet count (p < 0.01) indicative of a greater degree of hypersplenism . Leukopenic patients received a higher mean daily dosage of cephalosporins as compared with nonleukopenic patients . CONCLUSION: beta-Lactam antibiotics when administered in usually recommended dosages can induce leukopenia in patients with hepatic dysfunction . The probable mechanism is impaired hepatic metabolism of the beta-lactam antibiotics resulting in bone marrow suppression of white cell precursors from excessive antibiotic concentrations . The more severe the hepatic dysfunction, the greater the risk . We propose a reduction in dosages of beta-lactam antibiotics when used in patients with hepatic dysfunction . Finally, we raise the possibility that this adverse drug effect is more common than currently recognized by physicians.

J Pharmacol Exp Ther, 1993 Mar, 264(3), 1425 - 31
A potent inhibitory effect of erythromycin and other macrolide antibiotics on the mono-N-dealkylation metabolism of disopyramide with human liver microsomes; Echizen H et al.; Clinical observation has suggested that erythromycin (EM) may cause an elevation in plasma disopyramide (DP) concentrations and thereby cause potentially fatal arrhythmias in certain patients . To determine whether EM would interfere with the in vivo pharmacokinetics of DP and whether other macrolides would share this action with EM, the effects of EM and other macrolide antibiotics on the in vitro DP metabolism to its major metabolite, mono-N-dealkyldisopyramide, were studied with human liver microsomes obtained from eight patients who underwent partial hepatectomy . The mono-N-dealkylation of DP proceeded with a biphasic enzyme kinetic profile, suggesting that at least two distinct enzyme sites or components are involved in the DP metabolism in humans . The high- and low-affinity sites gave the mean (+/- S.D.) Km of 5.7 +/- 2.8 and 724.7 +/- 427.4 microM, and Vmax of 2.90 +/- 1.17 and 18.20 +/- 8.84 nmol/hr/mg protein, respectively . Because the mean intrinsic clearance (i.e., Vmax/Km) for the high-affinity site (i.e., 0.79 +/- 0.69 ml/hr/mg protein) was about 30 times greater than that for the low-affinity site (i.e., 0.03 +/- 0.01 ml/hr/mg protein), the high-affinity site was considered more important in the DP metabolism at its therapeutic concentrations (i.e., 2-5 micrograms/ml or 5-14 microM) . EM inhibited the high-affinity site activity in a noncompetitive manner with the mean Ki of 19.5 +/- 1.3 microM (n = 4) . An EM concentration associated with a 50% suppression of the DP metabolism at 30 microM (i.e., IC50) was 94 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

J Bacteriol, 1993 Mar, 175(6), 1847 - 52
The unstable melC operon of Streptomyces antibioticus is codeleted with a Tn4811-homologous locus; Yu TW et al.; The melC operon of Streptomyces antibioticus is unstable, undergoing frequent spontaneous deletions . All the delta melC mutants analyzed also lost 2-kb V1 DNA, which contained two open reading frames (ORFs) homologous to ORF4 (a putative oxidoreductase gene) and ORF5 (a putative AraC-type regulatory gene) of Tn4811 . The two ORFs may constitute an accessory unit of a different transposon.

Vestn Khir Im I I Grek, 1993 Mar-Apr, 150(3-4), 53 - 6
{The regional use of antibiotics in treating craniocerebral trauma and suppurative complications}; Domanskaia IA et al.; The authors used the intracarotid and subarachnoid methods of infusion of antibiotics for treatment of purulent meningitis, brain abscesses . The methods are considered to be fairly effective.

Clin Exp Rheumatol, 1993 Mar-Apr, 11 Suppl 8, S113 - 5
Antibiotics as disease modifiers in arthritis; Kloppenburg M et al.; The tetracyclines, especially minocycline, are supposed to have antiarthritic properties . Their efficacy has been tested in open clinical studies on RA patients . Recently a double-blind placebo-controlled trial was performed which revealed the antirheumatic properties of minocycline . The mode of action of the tetracyclines in arthritis is unknown, but could be linked to the immunosuppressive activity seen in vitro . The antiproliferative effect of minocycline in cloned synovial T-cells is demonstrated; moreover IFN-gamma production in cloned synovial T-cells is inhibited by minocycline.

Nippon Ganka Gakkai Zasshi, 1993 Mar, 97(3), 318 - 23
{Intraocular penetration of current antibiotics}; Miyao M et al.; We studied the intraocular penetration of 42 antibiotics in white rabbit eyes between 1980 to 1990 in our department . The parenteral route (intravenous, intramuscular): the ratios of maximum aqueous humor to serum level were 5.28-11.6% in penicillins (PCs), 5.95-20.17% in cephems and 13.4-30.27% in aminoglycosides (AGs) . The aqueous concentration of antibiotics reached a peak within 1/4-1 hour after injection . Oral administration: the ratios of aqueous to serum level were 8.52-20.6% in PCs, 3.62-20.11% in cephems, 22.8-75.8% in macrolides (MLs) and 6.38-23.6% in quinolones . The aqueous concentration of antibiotics reached a peak within 1-4 hours after oral administration . The ratio of aqueous to serum level was the highest in MLs . The aqueous level reached a peak faster and the ratio of aqueous to serum level was higher by injection than by oral administration.

Mol Microbiol, 1993 Mar, 7(6), 837 - 45
Stationary-phase production of the antibiotic actinorhodin in Streptomyces coelicolor A3(2) is transcriptionally regulated; Gramajo HC et al.; Production of actinorhodin, a polyketide antibiotic made by Streptomyces coelicolor A3(2), normally occurs only in stationary-phase cultures . S1 nuclease protection experiments showed that transcription of actII-ORF4, the activator gene required for expression of the biosynthetic structural genes, increased dramatically during the transition from exponential to stationary phase . The increase in actII-ORF4 expression was followed by transcription of the biosynthetic structural genes actIII and actVI-ORF1, and by the production of actinorhodin . The presence of actII-ORF4 on a multicopy plasmid resulted in enhanced levels of actII-ORF4 mRNA, and transcription of actIII and actinorhodin production during exponential growth, suggesting that actinorhodin synthesis in rapidly growing cultures is normally limited only by the availability of enough of the activator protein . bldA, which encodes a tRNA(Leu)UUA that is required for the efficient translation of a single UUA codon in the actII-ORF4 mRNA, was transcribed throughout growth . Moreover, translational fusions of the 5' end of actII-ORF4 that included the UUA codon to the ermE reporter gene demonstrated the presence of functional bldA tRNA in young, exponentially growing cultures and no increase in the efficiency of translation of UUA codons, relative to UUG codons, was observed during growth . The normal growth-phase-dependent production of actinorhodin in the liquid culture conditions used in these experiments appears to be mediated at the transcriptional level through activation of the actII-ORF4 promoter.

Proc Natl Acad Sci U S A, 1993 Feb 15, 90(4), 1172 - 8
Toward an estimation of binding constants in aqueous solution: studies of associations of vancomycin group antibiotics; Williams DH et al.; An approach toward the estimation of binding constants for organic molecules in aqueous solution is presented, based upon a partitioning of the free energy of binding . Consideration is given to polar and hydrophobic contributions and to the entropic cost of rotor restrictions and bimolecular associations . Several parameters (derived from an analysis of entropy changes upon the melting of crystals and from the binding of cell wall peptide analogues to the antibiotic ristocetin A) which may be useful guides to a crude understanding of binding phenomena are presented: (i) amide-amide hydrogen bond strengths of -(1 to 7) +/- 2 kJ.mol-1, (ii) a hydrophobic effect of -0.2 +/- 0.05 kJ.mol-1.A-2 of hydrocarbon removed from exposure to water in the binding process, and (iii) free energy costs for rotor restrictions of 3.5-5.0 kJ.mol-1 . The validity of the parameters for hydrogen bond strengths is dependent on the validity of the other two parameters . The phenomenon of entropy/enthalpy compensation is considered, with the conclusion that enthalpic barriers to dissociations will result in larger losses in translational and rotational entropy in the association step . The dimerization of some vancomycin group antibiotics is strongly exothermic (-36 to -51 kJ.mol-1) and is promoted by a factor of 50-100 by a disaccharide attached to ring 4 (in vancomycin and eremomycin) and by a factor of ca . 1000 by an amino-sugar attached to the benzylic position of ring 6 in eremomycin . The dimerization process (which, as required for an exothermic association, appears to be costly in entropy) may be relevant to the mode of action of the antibiotics.

Biochem Pharmacol, 1993 Feb 9, 45(3), 766 - 8
Polyene antibiotics inhibit superoxide-producing NADPH oxidase in a polymorphonuclear cell-free system; Capuozzo E et al.; We studied the effect of polyene macrolide antibiotics on the NADPH-dependent superoxide production induced by arachidonic acid in a cell-free system consisting of the membrane and cytosolic fractions obtained from bovine polymorphonuclear leukocytes . Preincubation of the membrane fraction with polyenes before addition of the soluble components of the reaction mixture resulted in a dose-dependent inhibition of superoxide production.

J Pharm Biomed Anal, 1993 Feb, 11(2), 121 - 30
Simple methods for the qualitative identification and quantitative determination of macrolide antibiotics; Danielson ND et al.; Pyrolysis-gas chromatography is shown to be a rapid straightforward method for the qualitative differentiation of the macrolide antibiotics erythromycin, oleandomycin, troleandomycin, spiramycin and tylosin . Organic salts do not interfere and identification of erythromycin and troleandomycin in commercial products is viable . Spectrophotometric quantitation of these same five antibiotics after reaction with concentrated sulphuric acid is studied at about 470 nm . Reaction conditions such as acid concentration, time and temperature are provided . The sugar moieties of the antibiotics are proposed as the reactive sites . Detection limits are about 0.2-1.0 microg ml-1 {corrected} and analysis of pharmaceutical products should be possible.

J Antibiot (Tokyo), 1993 Feb, 46(2), 280 - 6
Isolation and characterization of four polyether antibiotics, X-14889A, B, C, and D, closely related to lysocellin and the ferensimycins; Westley JW et al.; Streptomyces sp . X-14889 (NRRL 15517) has been found to produce a number of novel polyether antibiotics and an orange pigment . One of the antibiotics, X-14889B (3) was identified as ferensimycin A, which in turn is an isomer of the well-studied polyether antibiotic, lysocellin (1) . Of the three other antibiotics, X-14889C (4) is a lower homolog of ferensimycin A and antibiotics X-14889A (2) and D (5) which are respectively the descarboxy and anhydro-descarboxy forms of this same molecule . The latter compound, X-14889D is of interest as it contains an ether bridge across the terminal tetrahydrofuranyl ring in an analogous relationship to that reported earlier for antibiotics X-14873A (6) and G.

J Antibiot (Tokyo), 1993 Feb, 46(2), 255 - 64
AB023, novel polyene antibiotics . II . Isolation and structure determination; Bortolo R et al.; AB023, a complex of new polyene antibiotics, was isolated from a soil Streptomyces strain . The two main components, pentaene antibiotics AB023a and AB023b, were separated and purified by preparative chromatographic methods and their structures were determined by extensive NMR and mass spectrometric studies.

J Biomol Struct Dyn, 1993 Feb, 10(4), 709 - 26
Quantum chemical and molecular mechanics studies on the binding of stereoisomers of the oligopeptide antibiotics amidinomycin and noformycin to the minor groove of B-DNA; Sapse AM et al.; Ab initio calculations (Hartree-Fock) using the 6-31G basis set have been performed on two chiral oligopeptide antitumor antibiotics amidinomycin 5 and noformycin 6 . The latter are DNA minor groove binding agents related to the A.T recognizing netropsin 4 and distamycin 3 but, unlike the latter, bear stereocenters (two for 5 and one for 6) that may be expected to affect binding to the B-DNA receptor . Geometry optimized conformations, energies and distribution of electrostatic charges within the molecules were derived . The rotational barrier for bond C3-C6 in 6 was calculated to be ca . 6 kcal.mole-1 and the dipole moment for 6 was 7.69D and for 5 was 5.58D . The ab initio derived parameters of the geometry optimized conformations of the different possible stereoisomeric forms of 5 and 6 were used to interpret their different interactions with the minor groove of DNA at both A.T and G.C sequences and the results were compared with molecular mechanics calculations . The order of binding of the four stereoisomers of 5 at the preferred (A.T)n sequences by both ab initio and molecular mechanics calculations is 1S,3R > RR > RS > SS . The predicted energy differences for complexation with DNA of the other stereoisomers from that of 1S,3R are: RR (4.2%); RS (6.7%) and SS (21.5%) . In the case of noformycin the 4R structure binds more effectively than the enantiomer . Considerations of phasing in the computed distances between hydrogen bond donating sites in the DNA-bound antibiotics provide further insight into the binding processes . In the complexes of noformycin 6 the N-N1-N4 and N1-N5 distances (9.05 and 9.15 A respectively for 4R-6 and 9.23 and 9.26 A respectively for 4S-6) are close to the optimum value of 9.1 A for effective binding . In the case of amidinomycin 5 the best agreement with the optimum value occurs with the strongest binding diastereomer 1S,3R (N1-N3 = 8.91, N1-N4 = 9.41 A) . The unexpected result, consistent in both ab initio and molecular mechanics treatments, is that, in contrast to the cases of kikumycin 1 and anthelvencin 2, the natural 3S configuration of 5 and 4S of 6 do not confer maximal binding efficiency . This suggests that biogenetic factors in the generation of the oligopeptide antibiotics lead to maximum DNA binding in the cases of kikumycin and anthelvencin but not in the cases of amidinomycin and noformycin.

Orthopedics, 1993 Feb, 16(2), 247, 250 - 3
Radiologic case study . Antibiotic modified osteomyelitis; Morrissey D; The clinical and radiologic presentation of antibiotic-modified osteomyelitis closely resembles primary subacute pyogenic osteomyelitis . The widespread use of antibiotics has increased the incidence of this entity . When a patient is found to have a solitary bone lesion, a careful history should include inquiries regarding recent antibiotic therapy for any condition.

Gut, 1993 Feb, 34(2), 181 - 6
Development of a 14C-urea breath test in ferrets colonised with Helicobacter mustelae: effects of treatment with bismuth, antibiotics, and urease inhibitors; McColm AA et al.; A 14C-urea breath test analogous to its clinical counterpart is described for use in ferrets naturally or experimentally infected with Helicobacter mustelae . The test is performed within a sealed glass metabolism chamber through which air is drawn at a constant rate and expired breath collected into sodium hydroxide . Peak 14CO2 production occurred approximately 1 hour after substrate administration . Both inter- and intra-animal responses were highly reproducible, with mean coefficients of variation less than 10% . Other than enhancing peak 14CO2 levels very slightly, fasting had little influence on the response . In infant animals challenged with H mustelae, breath test activity increased linearly with the total count of culturable bacteria isolated from the antrum . Treatment of established infections with colloidal bismuth subcitrate (DeNol) for 4 weeks resulted in clearance of all detectable bacteria but retention of some breath test activity . Subsequent regrowth of bacteria was parallelled by an increase in the breath test response . Inclusion of amoxycillin and metronidazole in the treatment regimen, however, eradicated all the bacteria and almost totally eliminated 14CO2 production . This response parallels the clinically observed suppressive effect on H pylori achieved with bismuth alone relative to the total eradication seen with triple therapy . A single oral dose of the urease inhibitor, flurofamide, inhibited over 90% of the response for at least 24 hours . Acetohydroxamic acid was less effective . These findings suggest that in the ferret H mustelae model, breath test analysis can be a useful, non-invasive alternative to endoscopy for evaluation of agents affecting either growth of the organism or urease activity.

Chest, 1993 Feb, 103(2), 541 - 6
The effect of antibiotic therapy on recovery of intracellular bacteria from bronchoalveolar lavage in suspected ventilator-associated nosocomial pneumonia; Dotson RG et al.; Intracellular bacteria (ICB) within recovered cells (> 7 percent) obtained via bronchoalveolar lavage (BAL) have been described as predictive of subsequent positive quantitative protected specimen brush (PSB) cultures in patients not receiving antibiotics . To determine the effect of prior or current antibiotic therapy on ICB relative to subsequent PSB culture, we prospectively evaluated 49 consecutive episodes of clinically suspected ventilator-associated pneumonia in 36 patients . Three patient groups were defined based on antibiotic administration: group 1 (current antibiotics), n = 31, samples obtained from patients currently receiving antibiotics; group 2 (recent antibiotics), n = 5, samples obtained from patients who received antibiotics > 48 h but < 72 h prior to sampling; and group 3 (no antibiotics), n = 13, samples from patients receiving no previous antibiotics within 7 days prior to sampling . Overall, PSB cultures (> or = 10(3) cfu/ml) were positive in 14 of 49 (29 percent) samples . In group 1, 2 of 31 (6 percent) samples were positive while 5 of 5 (100 percent) samples in group 2, and 7 of 13 (54 percent) in group 3 were positive . The presence or absence of ICB accurately predicted both positive and negative PSB cultures in 43 of 49 episodes . Of 43 correct predictions, 34 were negative predictions (negative ICB, negative PSB culture) . The vast majority of these (29) were obtained from group 1, patients currently receiving antibiotics . In contrast, of nine positive predictions (+ICB, +PSB) virtually all (seven) occurred in group 3, patients receiving no antibiotics . In group 3, 13 of 13 PSB cultures were accurately predicted, either positive or negative, by the presence or absence of ICB . Of seven positive PSB cultures in groups 1 and 2, only 2 (28 percent) were accurately predicted by ICB . From both samples, the cultured organism was resistant to all administered antibiotics . These data suggest both prior and current antibiotic therapy reduces recovery of ICB from BAL and reduces predictive accuracy of ICB for subsequent positive PSB cultures . However, negative prediction by ICB for subsequent negative PSB cultures was good . In contrast, ICB obtained from patients not receiving antibiotics are highly predictive of subsequent PSB culture results, both positive and negative . We do not recommend BAL for evaluation of ICB in patients currently receiving antibiotics or with a recent history of antibiotic use.

J Bacteriol, 1993 Feb, 175(3), 623 - 9
Characterization of a broad-range disulfide reductase from Streptomyces clavuligerus and its possible role in beta-lactam antibiotic biosynthesis; Aharonowitz Y et al.; Streptomyces clavuligerus is a potent producer of penicillin and cephalosporin antibiotics . A key step in the biosynthesis of these beta-lactam compounds is the cyclization of the thiol tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N by the enzyme isopenicillin N synthase (IPNS) . However, bis-ACV, the oxidized disulfide form of the tripeptide, is not a substrate for IPNS . We show here that S . clavuligerus possesses an NADPH-dependent disulfide reductase of broad substrate specificity that efficiently catalyzes the reduction of disulfide bonds in bis-ACV and in other low-molecular-weight disulfide containing compounds and proteins . The disulfide reductase comprises two protein components, a 70-kDa reductase consisting of two identical subunits, and a 12-kDa heat-stable protein reductant . The structural and functional properties of the disulfide reductase resemble those of the thioredoxin class of oxidoreductases . When the disulfide reductase system is coupled with IPNS, it quantitatively converts bis-ACV to isopenicillin N . These findings suggest that the disulfide reductase may play a role in the biosynthesis of penicillins and cephalosporins in streptomycetes . We also show here that S . clavuligerus lacks glutathione reductase and have previously reported that Streptomyces species do not contain glutathione . This disulfide reductase may therefore be important in determining the thiol-disulfide redox balance in streptomycetes.

Antimicrob Agents Chemother, 1993 Feb, 37(2), 199 - 202
Low neurotoxicity of LJC 10,627, a novel 1 beta-methyl carbapenem antibiotic: inhibition of gamma-aminobutyric acidA, benzodiazepine, and glycine receptor binding in relation to lack of central nervous system toxicity in rats; Hikida M et al.; The toxicity of LJC 10,627 to the central nervous system of rats was evaluated by examining the effects of the compound on gamma-aminobutyric acidA, benzodiazepine, and glycine receptor binding in rat synaptic membranes and on the induction of behavioral convulsions by intraventricular administration to rats . The concentrations of this compound needed to inhibit specific {3H}muscimol binding, specific {3H}diazepam binding, and specific {3H}strychnine binding were greater than those of imipenem, as demonstrated by the 50% inhibitory concentrations (IC50S of LJC 10,627, greater than 10 mM for each; IC50S of imipenem, 0.6, 1.9, and 0.2 mM, respectively) . These results reflect the fact that LJC 10,627 does not evoke severe convulsions or cause death, even when it is administered intraventricularly at a high dose (300 micrograms per rat), and suggest that the low neurotoxic potential of LJC 10,627 may be attributed to the chemical structure of this compound, which has a methyl radical at the 1 beta site and a triazolium radical at the side chain of the second site.

J Pharm Sci, 1993 Feb, 82(2), 162 - 6
Effect of aggregation on the kinetics of autoxidation of the polyene antibiotic amphotericin B; Lamy-Freund MT et al.; We have previously studied the autoxidation of the polyene antibiotic amphotericin B (AB) . In this paper we describe the dependence of the kinetics of autoxidation on the aggregation state of the antibiotic . Autoxidation, which is involved in drug inactivation and has been suggested to play a role in the mechanism of drug action, was assessed through the reaction of formed radicals with the spin label Tempol (2,2,6,6-tetramethyl-4-hydroxy-N-oxylpiperidine) by following the loss of the electron spin resonance signal, as previously described, and by oxygen consumption . Two types of AB (I and II) were used, the former being obtained by further purification of the latter . The kinetics of autoxidation were compared for aggregates formed by the antibiotic . Differences in aggregation state for both type I and type II AB were observed between monomeric, borax-complexed, and preparations in water containing variable proportions of dimethyl sulfoxide (DMSO) by optical absorption and circular dichroism (CD) spectra . On the other hand, although the suspensions of type I and type II AB in water-10% DMSO did not differ in their optical properties, they could be distinguished by quasielastic light scattering experiments, type II yielding smaller aggregates . It is proposed that the lack of difference in optical and CD spectra are due to the similarity of the microenvironments in both aggregates . In contrast, the borax complex of both type I and type II AB yielded similar optical and CD spectra and quasielastic light scattering behavior, indicating that complexation led to similar aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)

Zhonghua Wai Ke Za Zhi, 1993 Feb, 31(2), 122 - 3
{Purulent ventriculitis treated by continuous perfusion with antibiotic fluid}; Liu S; 24 cases of purulent ventriculitis were treated by perfusion with antibiotic fluid were reported . Two tubes were mounted, one for continuous drip in and the other for drain out . The results showed that it is more effective than ordinary antibiotic injection and/or single tube drainage . The cure rate may be promoted if effective antibiotic were used early.

Neurol Res, 1993 Feb, 15(1), 63 - 7
Brain abscess treated by continuous antibiotic perfusion: technical note; Mahmood A et al.; Between 1982 and 1988, eleven patients with brain abscess were treated by craniotomy and continuous closed system antibiotic irrigation . By the use of this technique, repetitive abscess aspirations were not necessary.

Int J Immunopharmacol, 1993 Feb, 15(2), 163 - 73
In vitro stimulation of polymorphonuclear cell adhesion by ribomunyl and antibiotic + ribomunyl combinations: effects on CD18, CD35 and CD16 expression; Hbabi L et al.; Several functions of polymorphonuclear cells (PMNs) require adhesion to occur . Various membrane proteins' functions such as CD18 (beta 2 chain of integrin), CD35 (CR1) and CD16 (F c gamma Receptor III) participate in adhesion . In vivo treatment with Ribomunyl (R), an immunomodulating agent, was shown to enhance adhesion and migration of PMNs . To explore the direct effect of R on PMNs, cells from healthy subjects were treated in vitro with R . A significant increase of PMN adhesion and expression of CD18 and CD35 molecules were observed with 50 and 100 micrograms/ml of R after 2 h incubation . However, R-treatment decreased the PMN reactivity towards anti-CD16 (F c gamma RIII) monoclonal antibody . The effect of R on adhesion and membrane molecule expression was independent of the presence of serum and of polymixin B . Thus, this effect cannot be due to lipopolysaccharide (LPS) contaminants and does not require interactions with serum components . In previous studies, it was shown that in vitro amoxicillin increased some PMN functions whereas josamycin decreased them . The in vitro incubation of PMNs with R and amoxicillin (100 micrograms/ml) potentiated the positive effect of amoxicillin on adhesion and the antibiotic counterbalanced the negative effect of R on CD16 expression . In addition, R compensated the negative effect of josamycin (100 micrograms/ml) on PMN adhesion and on CD18 and CD35 expression . This study indicates: (1) the direct effect of R on PMN adhesion and on expression of molecules involved in adhesive-mediated functions, and (2) the beneficial effect of the association of R with antibiotics which can stimulate PMN activity.

J Calif Dent Assoc, 1993 Feb, 21(2), 46 - 50
How to use antibiotics effectively; Pallasch TJ; Management and control of infectious disease is complicated by a number of variables . This paper reviews factors in choosing an antibiotic; the pharmacokinetic principles of absorption, distribution, metabolism and excretion; duration of therapy; and major causes of failure of antibiotic therapy.

Int J Immunopharmacol, 1993 Feb, 15(2), 175 - 83
Immunomodulating activities of orally administered SMANCS, a polymer-conjugated derivative of the proteinaceous antibiotic neocarzinostatin, in an oily formulation; Suzuki F et al.; Immunomodulatory effects of oily formulated SMANCS, a polymer conjugated derivative of the proteinaceous antibiotic neocarzinostatin, after oral administrations to mice was investigated . The oral administrations of SMANCS, dissolved in medium-chain triglyceride containing phosphatidylcholine and polyglycerine dioleate (oily SMANCS), resulted in: (1) augmentation of NK cell activity in naive mice, (2) activation of macrophage cytostasis in naive mice, (3) enhancement of the generation of cytotoxic T-lymphocytes in mice immunized with allogeneic lymphocytes, (4) production of circulating interferon in naive mice, and (5) increase of delayed-type hypersensitivity response in mice immunized with sheep red blood cells . The degree of immunomodulation orally stimulated with oily SMANCS was similar to that of the immunomodulation induced by i.v . or i.p . administrations of aqueous formulated SMANCS (aqueous SMANCS) . Although SMANCS is a protein drug that may be digestable by various enzymes present in the stomach, in the present study immunomodulating activities of SMANCS were clearly demonstrated when an oily formulation of the compound was administered to mice orally . Since aqueous SMANCS administered parenterally and oily SMANCS administered orally exhibit the same immunomodulatory activities and the former has demonstrated antitumor activity in man and animals, the latter may possess this same antitumor activity.

Biochem Biophys Res Commun, 1993 Jan 29, 190(2), 362 - 70
DNA binding and cleavage of a novel antitumor antibiotic dynemicin A: detection of binding and cleavage sites by exonuclease III digestion and alkali-induced cutting reactions; Arakawa T et al.; We found here that dynemicin A effectively breaks DNA strands under alkaline pH condition . Binding of dynemicin A to double-stranded DNA clearly interrupts the digestion reaction of exonuclease III . The DNA association sites of dynemicin A correspond considerably well to its cleavage sites . Dynemicin A seems to intercalate preferentially into the relaxed region of the DNA double helix . On the other hand, the alkali-product of dynemicin A was chromatographically identified with dynemicin N, suggesting a DNA cleavage mechanism similar to the reductant- and light-induced activation systems of dynemicin A . In order to detect drug binding to the relaxation structure in the DNA duplex, the present exonuclease III-digestion-stop-sequence method is useful.

N Z Med J, 1993 Jan 27, 106(948), 13 - 4
Antibiotic protocol for appendicectomy--costs and benefits of single dose therapy; Coldham GJ et al.; AIMS . To examine possible savings from the introduction of an antibiotic protocol for one surgical procedure and to define antibiotic charting techniques . METHODS . An antibiotic policy for patients undergoing an appendicectomy was instituted in the surgical unit at North Shore Hospital to examine possible savings and to define antibiotic charting techniques . Depending on the macroscopic findings at surgery a third generation cephalosporin was used either as a single dose intraoperatively or for multiple doses postoperatively . RESULTS . The case notes of a control group of 55 patients were reviewed . This showed an average antibiotic cost per appendicectomy of $69.00 ($52.00) for nongangrenous nonperforated appendices (NGNPA) . During the study period 57 patients underwent appendicectomy at an average antibiotic cost of $51.00 ($32.00 for NGNPA) . This represented a 26% saving per patient during the study period and a 39% saving for those with NGNPA . CONCLUSIONS . The findings advocate the use of frequently updated guidelines for antibiotic use in surgical procedures . It reaffirms that medical staff must chart precisely as poor charting represents significant waste of expenditure in hospitals.

J Chromatogr, 1993 Jan 22, 629(2), 267 - 76
High-performance liquid chromatography-thermospray mass spectrometry of ten sulfonamide antibiotics . Analysis in milk at the ppb level; Abian J et al.; Ten sulfonamide antibiotics including sulfanilamide (SNL), sulfamethazine (SMZ), sulfamethizole (SMTZ), sulfachloropyridazine and sulfaquinoxaline (SQX), were analyzed by thermospray (TSP) mass spectrometry on-line with a high-performance liquid chromatography-UV detection system . Except for the pairs SMZ-SMTZ and sulfadimethoxine-SQX, the standards were resolved in both the UV and TSP profiles . Co-eluting compounds could be differentiated in TSP by their different relative molecular masses . The {M+H}+ ion was the base peak for all the standards except SNL, which showed an {M+NH4}+ ion . Collision-induced dissociation of the {M+H}+ ions afforded daughter ion spectra characterized by common ions at m/z 92, 108 and 156, and ions derived from the amine substituent ({MH-155}+) . TSP detection limits {signal-to-noise ratio (S/N) > 3} were below 20 ng (scan mode), 2 ng (selected reaction monitoring, daughter ions from {M+H}+) and 400 pg (selected ion monitoring) . UV detection limits were ca . 2 ng (S/N > 5) . Results obtained from the multi-residue analysis of spiked cow milk samples at the low ng/ml level are presented.

Am Surg, 1993 Jan, 59(1), 34 - 9
Injury severity dictates individualized antibiotic therapy in penetrating abdominal trauma; Griswold JA et al.; Antibiotics play a crucial role in reducing the risk of postoperative infection in patients suffering penetrating abdominal trauma . The infection rate for patients with these injuries ranges from 7% to 16% . Single agents with broad-spectrum activity have proven efficacy, but dosage and duration are still controversial . A prospective, double-blinded study was performed on 102 patients randomized to receive one of three antibiotics for a total of 12 hours: cefoxitin (3 doses, 31 patients); ceftizoxime (2 doses, 36 patients); or mezlocillin (3 doses, 35 patients) . Two distinct groups at risk for postoperative infection were evident depending on the severity of injury: Group A were those with no colon injury or a colon injury that could be repaired, no evidence of shock, or fewer than 3 organs injured; Group B were those requiring a colostomy, evidence of shock on presentation, or three or more organs injured . All comparisons of the patient populations receiving the different antibiotics showed the two groups to be equivalent . The mean penetrating abdominal trauma index for Group A was 8.8 and 28.2 for Group B . The overall infection rate for Group A was 10.3% and 42.3% for Group B . There was a significant increase in infection rate for all antibiotics except ceftizoxime in Group B compared with group A . The penetrating abdominal trauma index was significantly higher in all patients who developed infection for all antibiotics . In addition, if the surgical wound was closed primarily, patients with colon injuries developed wound infections 71% of the time, and those with small-bowel injuries did so 30% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

Annu Rev Med, 1993, 44, 385 - 93
Prophylactic antibiotics in surgery; Ludwig KA et al.; Prophylactic antibiotics can decrease the incidence of postoperative wound infections in indicated procedures . The accepted indications for administering prophylactic antibiotics have been clean-contaminated procedures and prosthesis insertion, but new indications are evolving that consider wound contamination together with anesthetic risk and relative duration of the operation . A prophylactic antibiotic is chosen on the basis of its activity against endogenous flora likely to be encountered, its toxicity, and its cost, in that order . Potent antibiotics used for serious infections are generally not used for prophylaxis . A maximum dose of a prophylactic antibiotic is given preoperatively so that effective tissue concentration is present at and after the time of incision . In the absence of infection, antibiotics should not be continued beyond the operative day . Regimens for specific procedures are discussed.

Microbios, 1993, 73(296), 173 - 84
Antifungal activity of Myxococcus species 1 production, physicochemical and biological properties of antibiotics from Myxococcus fulvus S110 (Myxobacterales); Daoud NN et al.; Chloroform extracts of the culture supernatant of a strain of Myxococcus fulvus isolated from soil were fungistatic and prevented germination of spores of Botrytis cinerea . The antibiotics were produced during the exponential phase of growth and the effects of altering medium composition are described . The activity was fractionated into neutral, acidic and basic fractions . The neutral fraction had a molecular weight of 244 and was tentatively identified as 11-phenyl-undecadiene-2-ol . The acidic fraction was primarily n-hexadecanoic acid . The basic fraction contained components {N-(2-phenylethyl)-acetamide, and compounds tentatively identified as 1-isoquinoline carbonitrile and substituted quinolines} which have not previously been described in the myxobacteria.

Clin Ther, 1993 Jan-Feb, 15(1), 169 - 79; discussion 168
Safety, efficacy, and cost savings in an outpatient intravenous antibiotic program; Williams DN et al.; We analyzed the costs of an outpatient intravenous (IV) treatment program using a broad-spectrum, third-generation cephalosporin . Fifty-six patients were treated for various infections in a hospital-based outpatient IV antibiotic program . The mean length of outpatient treatment was 7.4 days (range, 2 to 24 days) . Infections in 53 patients resolved successfully, with only 3 patients experiencing recurrence . Side effect were minimal, with no significant toxicities; one case of oral candidiasis and one case of rash occurred . Collectively, the 56 patients were treated for 286 days in the hospital and 414 days in an outpatient program . Costs were totaled on a weekly basis and divided by seven to arrive at a daily charge; the antibiotic most frequently prescribed was used as the representative regimen . The mean cost for each hospital day was $417 compared with $155 per outpatient day, a savings of $262 on a daily basis . We conclude that outpatient IV antibiotic therapy is safe and effective for a variety of infections in a wide range of patients and can contribute to substantial financial savings.

Arzneimittelforschung, 1993 Jan, 43(1), 71 - 3
Comparative stability of carbapenem and penem antibiotics to renal dehydropeptidase-I; Hikida M et al.; Comparison has been made on the stability of 4 carbapenems and 3 penems against porcine renal dehydropeptidase-I (DHP-I) . Evaluated were the carbapenems (5R,6S)-3-{{2-(formimidoylamino)ethyl}thio}-6-{(R)-1-hydroxyethyl} - 7-oxo-1-azabicyclo{3.2.0}hept-2-ene-2-carboxylic acid monohydrate, CAS 74431-23-5, in the following called FAC, (5R,6S)-3-{(S)-1-(acetimidoylpyrrolidin-3-yl)thio}-6-{(R)-1- hydroxyethyl}-7-oxo-1-azabicyclo{3.2.0} hept-2-ene-2-carboxylic acid, CAS 87726-17-8, in the following called AHC, (4R,5S,6S)-3-{{(3S,5S)-5-dimethylcarbamoylpyrrolidin-3-yl}thio}-6- {(1R)-1-hydroxyethyl}-4-methyl-7-oxo-1-azabicyclo{3.2.0}hept-2-ene-2- carboxylic acid trihydrate, CAS 96036-03-2, in the following called DHC . (1R,5S,6S)-2-{(6,7-dihydro-5H-pyrazolo{1,2-a} {1,2,4}triazolium-6-yl)thio}-6-{(R)-1-hydroxyethyl}-1-methyl-ca rbapen - 2-em-3-carboxylate, in the following called DHM, and the penems (5R,6S)-6-{(R)-1-hydroxyethyl}-7-oxo-3-{(R)-2-tetrahydrofuryl}-4-thia-1 - azabicyclo {3.2.0}hept-2-ene-2-carboxylic acid sodium salt, in the following called HTC, (5R,6S)-2-carbamoyloxymethyl-6-{(1R)-hydroxyethyl}-2-penem-3-carboxylic acid, in the following called CHC, (5R,6S)-6-{(R)-1-hydroxyethyl}-3-{(3S)-(cis-1-oxotetrahydrothiophen++ +-3-yl) thio}-7-oxo-4-thia-1-azabicyclo{3.2.0}hept-2-ene-2-carboxylic acid, in the following called HHC . According to the comparison of the Vmax/Km ratios, the order of stability of the compounds to hydrolysis by renal DHP-I was as follows: DHM >> DHC > HHC > AHC > HTC > CHC > FAC . From this result it is particularly noteworthy that DHM has extremely high stability against renal DHP-I.

Nephron, 1993, 63(1), 65 - 72
Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole; Vanholder R et al.; Twenty-three stabilized chronic uremic patients with no active or recent infection were treated for 10 days with either cefodizime (5 x 2 g intravenously, n = 10) or cotrimoxazole (960 mg orally b.i.d., n = 8) in order to evaluate the effects on the depressed polymorphonuclear metabolic response to phagocytic challenge; a separate group of 5 patients received placebo . Ex vivo evaluation in whole blood of energy delivery to the phagocytosis-associated respiratory burst activity in response to latex and zymosan challenge was determined by measuring hexose-monophosphate shunt NAD(P)H-oxidase-related glycolytic activity . Cefodizime induced a statistically significant increase in the baseline-depressed glycolytic response for both latex and zymosan challenge, in contrast to cotrimoxazole and placebo . Depressed phagocytosis-related metabolic function in hemodialyzed patients was stimulated by cefodizime in recommended therapeutic doses but not by cotrimoxazole, the effect persisting for at least 2 weeks after the end of treatment.

Int Arch Allergy Immunol, 1993, 100(2), 128 - 34
Immunogenicity of various beta-lactam antibiotic-protein conjugates and cross-reactivity of the antibodies produced in guinea pig; Katsutani N et al.; Immunogenic properties of bovine serum albumin (BSA) conjugates of various beta-lactam antibiotics (ABs) and cross-reactivity of the produced antibodies were investigated in guinea pigs . Each AB-BSA conjugate was immunized with complete Freund's adjuvant . Following the second injection, AB-specific antibodies were detected with high titers . Produced antibodies showed concentration-dependent inhibition by the corresponding AB . Cross-reactivity between the produced antibodies and ABs was evaluated with two methods, i.e . by testing for reactivity with the various AB-ovalbumin conjugates, and by assaying for inhibition of enzyme-linked immunosorbent assay (ELISA) by the various ABs . The latter method could detect minor cross-reactions more sensitively than the former one . The results suggested that similarity of the acyl side chain of a cephalosporin nucleus or a penicillin nucleus contributes to immunological cross-reactivity.

J Antibiot (Tokyo), 1993 Jan, 46(1), 162 - 6
Sandramycin, a novel antitumor antibiotic produced by a Nocardioides sp . II . Structure determination; Matson JA et al.; The structure of sandramycin, a novel antitumor antibiotic, was established by spectroscopic analysis and chiral chromatography of its acid hydrolysate . It was determined to be a cyclic decadepsipeptide with a two-fold axis of symmetry and 3-hydroxyquinaldic acid as an appended chromophore.

Infect Control Hosp Epidemiol, 1993 Jan, 14(1), 21 - 8
Electronic surveillance of antibiotic exposure and coded discharge diagnoses as indicators of postoperative infection and other quality assurance measures; Hirschhorn LR et al.; OBJECTIVES: To assess postoperative exposure to parenteral antibiotics and coded discharge diagnoses of infection as markers of nosocomial infection, postoperative morbidity, and potentially inappropriate antibiotic use after cesarean section . DESIGN: Retrospective cohort study to compare automated markers with the criterion of record review . SETTING: Tertiary care hospital . PATIENTS: Women admitted to a large teaching hospital after April 15, 1987, and discharged before October 1, 1989, who underwent a nonrepeat, nonelective cesarean section and had received prophylaxis with a cephalosporin . METHODS: Antibiotic exposure and discharge diagnosis codes were obtained from a large electronic hospital data base . A sample of charts was reviewed to determine the presence of infection, other postoperative complications, and postoperative antibiotic exposure . RESULTS: A total of 2,197 women who had undergone a nonrepeat nonelective cesarean section were included in the study cohort . These women were assigned to 6 subgroups based on postoperative antibiotic exposure status and discharge codes suggesting endometritis, other postoperative infection, or no infection . Review of 457 records indicated that the overall infection rate was 9% . Eight percent of all the patients had a coded diagnosis for infection, and 16% received some parenteral antibiotics after the first postoperative day . Exposure to at least 2 days of parenteral postoperative antibiotics was the best marker by which to discriminate between infected and uninfected patients, with a sensitivity of 81%, a specificity of 95%, and a positive predictive value of 61% for detecting infection . The corresponding figures for coded diagnoses for infection had rates of 65%, 97%, and 74%, respectively . The combination of discharge codes and exposure to parenteral postoperative antibiotics resulted in a more accurate but less sensitive marker for nosocomial infections, with a positive predictive value of 94% and a sensitivity of 59% . The groups with discordant parenteral postoperative antibiotics exposure and discharge codes for infection were enriched for errors in coding, noninfectious morbidity, and unexplained antibiotic use . Less than 1% of the entire cohort had > or = to 2 days of parenteral postoperative antibiotics without any reason apparent in the medical record . CONCLUSIONS: Parenteral postoperative antibiotic exposure determined from automated pharmacy records correlated with the results of the more labor-intensive manual review of medical records for the identification of nosocomial infection . In addition, information on antibiotic exposure combined with coded discharge diagnoses provided a rapid screen to identify subgroups of patients with higher rates of infectious and noninfectious morbidity, unexplained antibiotic use, and errors in discharge coding . Information derived from electronic data bases created for administrative purposes may be useful as a marker for infectious complications, inappropriate antibiotic prescribing, and other issues related to total quality hospital monitoring.

Int J STD AIDS, 1993 Jan-Feb, 4(1), 33 - 40
Antibiotic susceptibility, serovars and auxotypes of gonococcal isolates in Stockholm . Relation to geographical origin of the infection; Bygdeman SM et al.; The antibiotic susceptibility, serovars and auxotypes were investigated in gonococcal strains isolated from all patients with gonorrhoea during one year in Stockholm, Sweden . The results were correlated to geographical origin of the infection . A total of 394 gonococcal strains were isolated from 392 patients, 135 (34%) women and 257 (66%) men . Beta-lactamase-producing gonococcal strains (PPNG) were isolated from 5% of the women and 16% of the men . Men had acquired their infection abroad more often than women (54% vs 33%) (P < 0.001) . The majority (81%) of the PPNG infections were imported . Some serovars and auxotypes were more common among imported strains than among indigenous ones . All strains were sensitive to spectinomycin and 2 strains had decreased susceptibility to norfloxacin and ciprofloxacin . Decreased susceptibility to benzylpenicillin, ampicillin, doxycycline and cefuroxime was related to the geographical origin of the strains with strains imported from regions other than Europe being the most resistant.

J Bone Joint Surg Br, 1993 Jan, 75(1), 32 - 5
Timing of antibiotic administration in knee replacement under tourniquet; Richardson JB et al.; Cephamandole levels in serum and drain fluid were measured in 32 knee replacement operations to determine the benefit of an intravenous dose of antibiotic at the time of tourniquet deflation . Concentrations of cephamandole in drain fluid were directly proportional to the serum concentration at the time of tourniquet release . A 'tourniquet-release' dose of antibiotic increased drain fluid concentration threefold.

Am J Dis Child, 1993 Jan, 147(1), 40 - 4
Ought 'standard care' be the 'standard of care'? A study of the time to administration of antibiotics in children with meningitis; Meadow WL et al.; OBJECTIVE--To determine the time from triage in an emergency department until administration of parenteral antibiotics in children with bacterial meningitis . RESEARCH DESIGN--Retrospective review of medical records and survey of medical subspecialists in infectious diseases and emergency medicine . SETTING--Emergency departments of two university-affiliated pediatric hospitals . PARTICIPANTS--All children with bacterial meningitis identified in medical records from 1987 to 1989 (N = 93) . MEASUREMENTS--For each child, the time from presentation to the emergency department until administration of antibiotics (AB time) was determined; when possible, time from triage to contact with a physician, from triage to lumbar puncture, and from lumbar puncture to administration of antibiotics was measured . We then surveyed specialists in both pediatric infectious diseases (n = 23) and pediatric emergency medicine (n = 54) as to their beliefs about AB time in children with meningitis . STATISTICAL ANALYSES--Mann-Whitney Rank Sum Test and Kruskal-Wallis Test . RESULTS--Median AB time was 2.0 hours (interquartile range, 1.25 to 3.33 hours) . Only one (1%) of 93 children received antibiotics within 30 minutes of presentation . Median time from triage until contact with a physician was 0.45 hour . Median time from lumbar puncture until antibiotics administration was about 0.5 hour . The estimates of median AB time differed significantly between emergency medicine (0.93 hour) and infectious disease (1.45 hours) experts, and estimates from both differed significantly from the median AB time (2.0 hours) actually observed . CONCLUSIONS--These data reveal that the usual and customary practice (ie, standard medical care) by qualified physicians may differ from opinions of standard medical care promulgated by medical experts . Even among experts there is a wide range of (mistaken) opinions about standard medical care . Insofar as jurors in medical malpractice cases are instructed to consider what physicians "ordinarily do in similar circumstances," a data-based definition of "standard" medical care should supplant anecdotal testimony by individual expert witnesses.

MD Comput, 1993 Jan-Feb, 10(1), 17 - 22
Development of an automated antibiotic consultant; Evans RS et al.; Physicians frequently need to order antibiotic therapy before the results of bacterial cultures and antibiotic susceptibility tests are available . Therapy selected empirically should be chosen on the basis of the most recent information about probable pathogens and their susceptibility to various drugs . We have developed a series of computer programs to help physicians identify the antibiotic regimens with the highest probability of acting against the pathogens that are most likely to be present at suspected sites of infection in individual patients . This automated antibiotic consultant is now available on our hospital information system . A comparison of the antibiotic regimens suggested by the computer with those indicated by cultures and susceptibility tests showed that the computer suggested an appropriate regimen for 717 of 761 culture events (94%).

J Clin Invest, 1993 Jan, 91(1), 38 - 45
Protection by antibiotics against myeloperoxidase-dependent cytotoxicity to lung epithelial cells in vitro; Cantin A et al.; Myeloperoxidase, in the presence of noncytotoxic concentrations of H2O2, was used to induce cytotoxicity to the lung epithelial cell line, AKD . When the cationic aminoglycosides, tobramycin and gentamicin were added to the cells in the presence of myeloperoxidase and H2O2, cytotoxicity was completely inhibited . In addition, tobramycin prevented cytotoxicity induced by cystic fibrosis sputum and H2O2 . Protection against myeloperoxidase and H2O2 was also observed with the thioether-containing antibiotics, ticarcillin and ceftazidime, but at higher concentrations than with the aminoglycosides . Analysis of spectral properties, dimethylsulfoxide-mediated reduction, and ethyl acetate/NaCl partitioning, demonstrated that aminoglycosides converted HOCl to hydrophilic noncytotoxic chloramines, but were unable to prevent the oxidation of sulfhydryls and methionine by HOCl . In contrast, ticarcillin and ceftazidime were highly effective inhibitors of HOCl-mediated sulfhydryl and methionine oxidation . These results suggest that aminoglycosides protect lung epithelial cells against myeloperoxidase-dependent oxidant injury by binding to anionic cell surfaces and converting HOCl to hydrophilic noncytotoxic chloramines, whereas penicillins and cephalosporins are potent HOCl scavengers capable of protecting critical extracellular molecules against oxidation.

J Bone Joint Surg Br, 1993 Jan, 75(1), 111 - 4
Experimental implant-related osteomyelitis treated by antibiotic-calcium hydroxyapatite ceramic composites; Korkusuz F et al.; The efficacy of locally implanted antibiotic-calcium hydroxyapatite ceramic composites was investigated for the treatment of experimentally produced, implant-related osteomyelitis in rats . High concentrations of antibiotics were detected at the site of infection and bacteria were eradicated without removal of the metal implants . Parenteral antibiotics and surgical debridement, alone or in combination with antibiotic-impregnated acrylic bone cement, all failed to eradicate the infections.

Wien Med Wochenschr, 1993, 143(7-8), 199 - 200
{Antibiotic concentrations after intravenous and retrograde intravenous injections}; Schoop W et al.; In patients with peripheral arterial occlusive disease, it is difficult to attain an adequate antibiotic concentration in poorly perfused infected lesions . The antibiotic concentrations prevailing in the ulcer secretion with the different routes of administration were investigated in 7 patients . The patients received 1 g of cefotaxim on consecutive days: intravenously on the first day, intraarterially on the second day and by retrograde venous injection on the third day . Significantly higher concentrations in the secretion were found after retrograde venous antibiotic administration than after intravenous or intraarterial injection . Clinical experience up to now indicates that far better results of treatment can be attained if the antibiotic is administered by retrograde venous injection (in addition to the surgical measures required).

Wien Med Wochenschr, 1993, 143(7-8), 195 - 8
{Malum perforans diabeticorum: treatment with controlled circulatory blockade and regional intravenous administration of antibiotics}; Acevedo A et al.; Orthopedic deformations of the feet play an important role in the etiology of the foot ulcers of diabetic patients, together with neuropathy and vascular impairment . The employment of new techniques in the treatment of diabetic foot has considerably improved its prognosis . These are the transient circulatory blockade (TCB) and the regional intravenous antibiotic administration (RAA) . This paper reports on the usage of these techniques in the treatment of 24 diabetic patients, 8 women with ages between 41 and 75 (mean 54.7) years, and 16 men with ages between 41 and 75 (mean 59.3) years who were operated on 29 opportunities because of foot ulcer . Most of the patients had different grades of foot infection . Neuropathy was present in all cases and a distal type of arterial occlusion was diagnosed in 8 cases . Foot surgery was performed under regional i.v . anesthesia associated with regional i.v . injection of 1 g Cefotaxine (Calaforan) in 250 ml saline solution which was administered through the same butterfly needle used for the regional anesthesia . The drainage of the foot infection was performed simultaneously with the orthopedic correction of the foot deformities . All patients healed without complications attributable to the bone surgery . Patients operated upon while complicated with foot phlegmons remained longer (31 days) in the hospital than those without infection (18 days) . After a follow-up period of 4.7 (1 to 8) years there were 2 recurrencies and 3 patients developed new foot ulcers . All patients were using a normal, soft shoe . We conclude that the TCB and the RAA facilitate orthopedic surgery in diabetic patients with foot ulcers improving their life quality and prognosis.

Eur J Cardiothorac Surg, 1993, 7(7), 360 - 3; discussion 364
The outcome of antibiotic sterilised aortic homografts used in the Fontan procedure; Monro JL et al.; Between 1977 and 1988, 27 patients between the ages of 4 and 22 years (mean 8.9) underwent a Fontan procedure with the use of an antibiotic sterilised aortic homograft . There were 15 patients with tricuspid atresia, 9 with univentricular heart and 3 others . The homograft was anastomosed to a right-sided pulmonary artery in ten, to a left-sided main pulmonary artery in eight and in nine patients the homograft connected the right atrium to the right ventricle . There were five early deaths (18.5%) unrelated to the homograft and two late deaths at 7 and 10 years postoperatively . Five patients have required removal of the calcified obstructed homograft with no death . In three patients patches were inserted, but in two patients with good right ventricles a second homograft was inserted . In three of the re-operated patients the homograft lay directly behind the sternum and the femoral artery was exposed and in two of them the femoral artery was cannulated before the chest was opened to control haemorrhage . Of the patients 74% are alive up to 15 years later, 15 with their original homograft . Eight (57%) of those still have their original homograft more than 10 years post-operatively.

Adv Enzyme Regul, 1993, 33, 3 - 17
Studies on the mechanism of the cytotoxic action of the mitomycin antibiotics in hypoxic and oxygenated EMT6 cells; Sartorelli AC et al.; The mitomycin antibiotics, because of their preferential toxicities for hypoxic cells, have significant potential as adjuncts to ionizing radiation in the treatment of solid tumors . To gain information on the mechanism by which these agents exert their cytotoxicities to hypoxic and aerobic cells, the effects of MC, POR and several of their analogs were studied in EMT6 mammary carcinoma cells . The rate of uptake of POR by these cells was directly correlated with the cytotoxicity produced by this agent under both hypoxia and aeration . At equivalent concentrations, uptake of POR into hypoxic cells was more rapid than into aerobic cells . Hypoxic cells also accumulated the antibiotic in concentrations well in excess of that present in the extracellular medium, presumably as a result of reductive activation and covalent binding of POR to cellular structures . Such activation and binding occur to a much lesser degree in aerated cells, resulting in the rapid efflux of POR from these cells when the antibiotic is removed from the extracellular environment . To gain information on the reaction of POR with DNA, mono- and bis-adducts formed in EMT6 cells exposed to this agent were measured . Three major adducts were formed . Two were mono-adducts consisting of deoxyguanosine linked at its N2-position to the C-1 of POR and of 10-decarbamoyl POR . The third was a bis-adduct in which POR was cross-linked to two deoxyguanosines at their N2-positions . More adducts were formed in hypoxia than in air, and more bis-adducts were present in hypoxic cells . Simultaneous exposure of cells to both POR and DIC reduced the total adduct level and a new unknown adduct was formed, primarily under hypoxia . Several mitomycins were evaluated for their capacity to kill EMT6 cells and to produce DNA cross-links in both hypoxia and aeration . The number of cross-links required to produce a given amount of cell kill was similar, regardless of the mitomycin employed or the degree of oxygenation . The findings support the concept that DNA is a critical target in the action of the mitomycins and that cross-linking of the DNA creates an important lesion for cytodestruction.

Int J Technol Assess Health Care, 1993 Fall, 9(4), 580 - 7
Cost savings through technological change in the administration of antibiotics; Liaropoulos LL; Once-daily antibiotics (ODAs) represent a technological change in hospital processes that can lead to substantial savings of scarce resources . In a three-hospital prospective study, five antibiotics were administered to 58 patients suffering from infections classified by major body system . Savings ranged from 10.9% to 38%, depending on hospital organization, method of delivery, and daily dose . Per-unit price proved a poor indicator of hospital cost, as variable delivery costs for labor and materials ranged from 11.6% to 39.5% of total costs.

J Investig Allergol Clin Immunol, 1993 Jan-Feb, 3(1), 53 - 5
Two cases of toxic epidermal necrolysis caused by delayed hypersensitivity to beta-lactam antibiotics; Romano A et al.; The authors describe two cases of toxic epidermal necrolysis (TEN) caused by delayed hypersensitivity to semisynthetic penicillins . The first patient developed erythema of the lower limbs following an i.m . injection of ampicillin, which progressed to TEN as therapy was continued . Fever and eosinophilic leukocytosis were also present . In the second case, TEN developed following oral amoxicillin therapy, and was preceded by a diffuse, maculopapular eruption . In both cases, symptoms resolved with the prompt administration of steroids . Both patients underwent allergological testing: prick test and, if results were negative, intradermal tests with penicilloyl-polylysine (PPL), minor determinant mixture (MDM), penicillin, amoxicillin and ampicillin . Patch testing with penicillin, ampicillin and amoxicillin was also performed . Both patients developed positive reactions to the intradermal tests after 6 h, and to patch tests after 48-72 h (for ampicillin, amoxicillin and penicillin in the first case, and for ampicillin and amoxicillin in the second) . The lymphocyte transformation test (LTT), performed only in the first case, was positive for ampicillin . As these cases demonstrate, delayed hypersensitivity should be suspected in cases of drug-related TEN . Patch testing is a simple and useful allergological test for these types of cases.

Annu Rev Microbiol, 1993, 47, 875 - 912
Polyketide synthesis: prospects for hybrid antibiotics; Katz L et al.; Polyketides fall into two structural classes: aromatic and complex . The former are built mainly from acetate units through a reiterative process wherein the beta-carbonyl groups formed after each condensation cycle are left largely unreduced . Complex polyketides are composed of acetates, propionates, or butyrates, and the extent of beta-carbonyl reduction varies from one cycle to the next . Two themes for polyketide synthases are emerging . Aromatic PKSs are determined by four to six genes encoding mono- or bifunctional enzymes; one PKS complex is used for all synthesis steps . Complex PKSs are composed of several multifunctional polypeptides that contain enzymatic domains for the condensation and reduction steps; each domain is used at a unique step in the pathways, and the extent of beta-carbonyl processing depends on the functional domains operating at that cycle . Mutations rendering certain domains nonfunctional have been introduced into genes for complex polyketides, resulting in the production of novel molecules.

Gynecol Obstet Invest, 1993, 36(2), 102 - 7
Premature rupture of the membranes--aggressive versus conservative approach: effect of tocolytic and antibiotic therapy; Matsuda Y et al.; The purpose of this randomized, prospective study was to evaluate the efficacy of tocolytic and antibiotic therapy in the prolongation of pregnancy and neonatal outcome in the treatment of premature rupture of the membranes without clinical labor . Delivery was delayed for 48 h, 7 days and beyond 35 weeks of gestation in 87, 39 and 18%, respectively, of patients in the treated group (n = 39) compared with 50, 12 and 17% of patients in the nontreated group (n = 42) . The incidence of a low Apgar score (< 7 at 5 min), requiring artificial ventilation, and infectious morbidity was more common in the treated group than in the nontreated group (18 vs . 0, 41 vs . 17 and 39 vs . 17%, respectively) . There was no significant cost difference in survivors between the treated and nontreated groups, although the mothers in the treated group were significantly more expensive . From these observations, it appears that tocolysis and antibiotics are not effective in PROM cases.

Dermatology, 1993, 187(3), 193 - 6
Oral trimethoprim as a third-line antibiotic in the management of acne vulgaris; Bottomley WW et al.; Acne vulgaris usually improves with long-term oral antibiotic therapy; however, some patients fail or only partially respond to the commonly prescribed antibiotics . Only a proportion of these patients warrants treatment with isotretinoin suggesting a need for additional therapeutic options . We have therefore performed an open retrospective study of the efficacy of trimethoprim as a third-line antibiotic in the treatment of patients whose acne vulgaris failed to respond to at least 2 courses of antibiotics . A total of 56 patients were reviewed, who had all failed to respond adequately to a minimum of 2 courses of antibiotics . All patients received trimethoprim in a dosage of 300 mg twice daily for at least 4 months, unless it had been withdrawn due to side effects . Topically they were given 1% clindamycin lotion twice daily to the affected areas . The severity of the patient's acne was graded on the face, back and chest . The changes in acne grades were evaluated using non-parametric statistics (Wilcoxon matched pairs) . At 4 months there were significant improvements from the grades at initiation in all three sites (p = 0.005 or less) . Twenty-one patients remained on the treatment for 8 months, and a significant improvement in the changes of the acne grades remained (p = 0.02 or less) . Two patients had the trimethoprim stopped due to side effects . We can therefore recommend this regime as a third-line treatment in the management of acne.

Yao Xue Xue Bao, 1993, 28(4), 260 - 5
{Antitumor effect of the immunoconjugate composed of antibiotic C1027 and Fab fragment from a monoclonal antibody directed against human hepatoma}; Li JZ et al.; Antibiotic C1027, a macromolecular peptide with highly potent cytotoxicity to cultured cancer cells, was conjugated to monoclonal antibody 3A5 and its Fab fragment separately using SPDP as the linker agent . McAb 3A5, identified as IgG1, was directed against human hepatoma BEL-7402 cells . By ELISA, McAb 3A5 and the Fab fragment were strongly reactive with hepatoma cells and weakly reactive with KB cells . Determined by clonogenic assay against hepatoma BEL-7402 cells, the IC50 values for McAb-C1027, Fab-C1027 and C1027 were 4.2 x 10(-14), 8.6 x 10(-16) and 6.5 x 10(-16) mol.L-1, respectively . Fab-C1027 was 49-fold more potent than McAb-C1027 in cytotoxicity . Moreover, Fab-C1027 was 160-fold more potent in cytotoxicity to hepatoma cells than to KB cells, indicating selective cytotoxicity of Fab-C1027 conjugate to the target cells . Therapeutic effect of the conjugate was evaluated with hepatoma BEL-7402 xenograft in nude mice . After subcutaneous transplantation of the tumor, treatment started on day 3, iv, with equivalent dose of C1027, 0.1 mg.kg-1 x 6 . Fab-C1027 and free C1027 inhibited tumor growth by 85% and 59%, respectively . Fab-C1027 conjugate showed more marked antitumor effect in vivo than free C1027.

Z Gesamte Inn Med, 1993 Jan, 48(1), 18 - 22
{Bile composition and antibiotic excretion . Observations with T-drainage}; Rosenthal RJ et al.; Patients comparable in disease, therapy and serum bilirubin concentration were either treated with mezlocillin intravenously or not at all . The bile of each patient was collected either from a T-drainage or from a percutaneously placed drainage into the bile ducts . The concentrations of GGT and AP, which were liberated by destroyed liver cells, and of bilirubin and mezlocillin, which were secreted actively, were analysed . Those patients who had normal serum bilirubin concentrations had a significantly higher biliary bilirubin excretion than those with high serum bilirubin level . The maximum excretion was after 4 hours . While the biliary concentration of bilirubin decreased, the concentration of secreted mezlocillin increased . Due to destroyed liver cells those patients with pathologically elevated blood bilirubin levels had a 50-fold lower mezlocillin excretion than those with normal blood values.

Scand J Infect Dis, 1993, 25(6), 779 - 82
Antibiotic susceptibility of Mycobacterium marinum; Forsgren A; A radiometric respirometric technique (Bactec) which is highly standardized for Mycobacterium tuberculosis was used for antibiotic susceptibility testing of clinical isolates of M . marinum . Ciprofloxacin, clarithromycin, rifampicin and trimethoprim/sulfamethoxazole were effective at clinically relevant concentrations . Doxycycline, erythromycin and roxithromycin were ineffective . These in vitro results are discussed in relation to documented clinical experience.

Neurochirurgie, 1993, 39(6), 380 - 4
{Comparative pharmacokinetics of antibiotics in blood, csf and brain}; Redondo A et al.; The Knowledge of the antibiotic's cerebral diffusion is essential to define a of neurosurgical antibioprophylaxis' strategy . Without references in the medical world-literature, we've decided to compare the pharmacological kinetics in the blood, the cerebrospinal fluid and the sound cerebral tissue of common used molecules in neurosurgery that is to say: amoxicillin, cefamandole, metronidazole and pefloxacin . The results show that the cerebral levels of metronidazole and pefloxacine are rapidly high with an extended duration (> 10 times the M.I.C . of the sensitive bacteriae), but the tissue penetration of amoxicillin is hazardous and shot-duration for cefamandole (undosable after 3 hours).

Acta Univ Palacki Olomuc Fac Med, 1993, 136, 45 - 7
Local application of antibiotics in treatment of cerebral abscess; Kala M et al.; The authors evaluate 61 patients treated for cerebral abscess . These patients were divided into 2 groups . The first group consisted of 42 patients who had the cavity left after the removal of the abscess irrigated with an antibiotic during the surgery . The other group of 19 patients were treated without this antibiotics . Only 2 patients of the first group (i.e . 4.7%) died as against the 6 deaths (i.e . 31.5%) in the other group . This result indicates the beneficial effect local administration of antibiotics has in treating cerebral abscess . This observation should however be checked on a larger series of patients.

Probl Khig, 1993, 18, 105 - 14
{The inhalational toxicity of the antibiotic preparation Bactericin for plant protection}; Khalkova Zh et al.; The acute and subacute inhalation toxicity of a new Bulgarian antibiotic preparation "Bactericin" for plant protection is examined . It is meant for the treatment of seeds from tomatoes before sowing . The inhalational toxicity is evaluated by a complex of toxicometric, integral, behavioural, clinic-laboratory, biochemical and histological methods . The maximum concentration reached by dispersing is 40 mg.m-3 . In the condition of acute (unrepeated exposure) and subacute (60 exposure) the concentration of 40 mg.m-3 causes no lethality, symptoms of intoxication and toxic effects in the organism of white rats therefore it could be accepted as not operative . The preparation conceals no danger of acute and chronic inhalational poisonings when working with the latter . On the basis of the performed investigations and bearing in mind, that the preparation is in the group of the antibiotics, a proposal is made for the purpose of orientation MAG in the air of the working zone -0.5 mg.m-3.

Aten Primaria, 1993 Jan, 11(1), 37 - 9
{Intervention for improving the quality of antibiotic prescription in a basic health area}; Casado Zuriguel I; OBJECTIVE . To evaluate the effectiveness of corrective measures introduced in a health area (HA) to improve the way antibiotics (AB) are prescribed . DESIGN . Intervention study, with a control . SITE . Two HAs: Cervera and Tarrega . The intervention was carried out in the first; the second serving as the control group . PATIENTS OR OTHER PARTICIPANTS . All the doctors in both areas' primary care teams (PCT) . INTERVENTION . Monographic sessions of the PCT during June and October, 1991, analysed consecutively the following, which had taken place in the health area during 1990: the quality control methodology applied to the prescription; the quality indicators in the prescription--among them its classification by intrinsic value (IV)--; and the general level of prescription with the proportion of ABs prescribed . MAIN MEASUREMENTS AND RESULTS . The pharmaceutical listing of the 100 most prescribed drugs in relation to the number of containers were used as a data source for evaluating the November, 1990, AB prescription; with a re-evaluation in November, 1991, after the introduction of the corrective measures . Significant reductions could be observed in the health area where the intervention took place, both in the percentage of low IV drugs prescribed (-10.8%) and of intramuscular injections used (-23.5%) . In the area used as the control group, there were no variations . CONCLUSIONS . The effect of the intervention on the improvement in the way ABs were prescribed, was clear.

Vestn Khir Im I I Grek, 1993 Jan-Feb, 150(1-2), 29 - 32
{Indirect lymphotropic antibiotic therapy in the treatment of destructive appendicitis}; Drachevskii NP et al.; The lymphotropic infusion of antibiotics through the Brun point in combination with Dibazol to patients operated upon for acute gangrenous and perforating appendicitis has not only antiinflammatory action, but also stimulates the immunobiological non-specific reactivity of organism and reduces lethality from 3.5% to 0.41% and makes time of the hospital and ambulatory treatment 10 days shorter . The amount of suppurative complications was reduced from 62% to 18.3%.

Biophys J, 1993 Jan, 64(1), 92 - 7
Inactivation by ionizing radiation of ion channels formed by polyene antibiotics amphotericin B and nystatin in lipid membranes: an inverse dose-rate behavior; Barth C et al.; The phenomena reported are part of a study about the effects of ionizing radiation on membrane transport . We found that the conductance of lipid membranes in the presence of the polyene-antibiotics nystatin or amphotericin B is reduced to virtually zero following irradiation . Ion channels formed by these substances seem to represent extremely sensitive structures being inactivated by radiation doses in the range of a few Centigray (1 cGy = 1 rad) at sufficiently small dose rates . Inactivation shows a so-called inverse dose-rate behavior, i.e., at constant radiation dose the effect increases with decreasing dose rate . Similar to radiation-induced lipid peroxidation the phenomenon may be understood on the basis of a radical chain mechanism initiated by free radicals of water radiolysis . The process--via peroxidation of the polyene part of the molecules--is suggested to modify the hydrophobic exterior and to destabilize the barrel-like structure of the ion channels.

Clin Mater, 1993, 13(1-4), 149 - 54
The efficacy of controlled antibiotic release for prevention of polyethyleneterephthalate- (Dacron-) related infection in cardiovascular surgery; Karck M et al.; Infection of prostheses containing polyethyleneterephthalate (Dacron) remains a dreaded complication in cardiovascular surgery despite perioperative antibiotic (AB) prophylaxis . Dacron, which is widely applied as a fabric for manufacturing vascular prostheses and also the sewing rings of artificial heart valves, remains a source for infection once implanted in the body . In order to increase the AB concentration in Dacron, an experimental study including topical application of the gentamicin derivative EMD 46/217 and fibrin sealant (F) as AB carrier was initiated . In-vitro pretreatment of Dacron with the gentamicin derivative and F was followed by constant AB release for three weeks . In a subsequent animal study, four Dacron rings with different pretreatments were implanted in the descending aorta of ten pigs after direct contamination with 10 8 Staph . aureus solution . One ring was pretreated with the AB/F compound, a second ring with the AB alone . Ring 3 (no pretreatment) and ring 4 (F alone) served as controls . After one week, the Dacron rings and their corresponding implantation sites were asserved for measurement of AB content and for culture . The AB content of AB/F rings was 24.99 +/- 7.16 mug/g wet weight, while Dacron rings pretreated with the AB alone contained no measurable drug amounts, with the exception of one specimen (0.5 mug/g)(AB/F versus AB rings: P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Health Trends, 1993, 25(3), 84 - 7
Prophylactic antibiotics at caesarean section do not reduce costs; Keane D et al.; A prospective audit of 200 patients was undertaken to determine the effectiveness of prophylactic antibiotics at caesarean section in reducing the cost of postnatal care . The main outcome measures were the cost-effectiveness of this treatment in reducing the cost of care and incidence of infection . The results show that the routine administration of prophylactic antibiotics had no significant effect on infection rates, the prescribing of puerperal antibiotics or the duration of stay in the postnatal period . The total cost of antibiotics in the prophylaxis group was over four times that in the non-prophylaxis group . The results of this study suggest that routine administration of antibiotics at caesarean section does not reduce the costs of care in the puerperium.

Biochemistry, 1992 Dec 8, 31(48), 12076 - 82
DNA sequence selectivities in the covalent bonding of antibiotic saframycins Mx1, Mx3, A, and S deduced from MPE.Fe(II) footprinting and exonuclease III stop assays; Rao KE et al.; DNA sequence selectivities in the covalent binding of the antitumor antibiotic saframycins Mx1, Mx3, A, and S have been determined by complementary strand MPE.Fe(II) footprinting and exonuclease III stop assays on two different 545 and 135 base pair long HindIII/RsaI restriction fragments of pBR322 DNA . Saframycins Mx1, Mx3, A, and S recognize primarily 5'-GGG sequences . All four antibiotics also recognize 5'-GGPy sequences, however a cytosine is preferred over a thymine at the 3'-end of this recognition site in all cases . Saframycins Mx1, Mx3 and S, which possess the OH leaving group, also recognize the 5'-CCG sequence, in contrast to saframycin A, which contains the CN leaving group . In contrast, the OH-containing saframycins also recognize the 5'-CTA sequence . Saframycins Mx2, B and C, which lack the critical CN or OH leaving group, do not show any footprints on the restriction fragments examined in this study . The measured binding site size for all four antibiotics is three base pairs . The exonuclease III stop assay independently confirmed the formation of a covalent bond and the strong preference of the antibiotics for 5'-GGG and 5'-GCC sequences . The latter enzyme assay also suggests that the 5'-terminal or central G of the triad binding site is the base to which reversible covalent attachment of the antibiotic takes place.

Aliment Pharmacol Ther, 1992 Dec, 6(6), 751 - 8
Short report: omeprazole plus antibiotic combinations for the eradication of metronidazole-resistant Helicobacter pylori; Bell GD et al.; Twenty-eight Helicobacter pylori-positive patients with metronidazole-resistant isolates and 25 with metronidazole-sensitive isolates were treated for 14 days with 40 mg omeprazole nocte plus 500 mg amoxycillin t.d.s . Eradication of H . pylori, defined as absence of the organism one month after cessation of treatment, was assessed using the {14C}urea breath test . The eradication rate in patients with metronidazole-resistant isolates was 14/28 (50%) while that in patients was metronidazole-sensitive isolates was 12/25 (48%) . In contrast to these encouraging eradication rates, very poor results were obtained with a 7-day course of omeprazole (40 mg nocte) in combination with erythromycin ethylsuccinate (500 mg q.d.s.) and tripotassium dicitrato bismuthate tablets (120 mg q.d.s.) . The latter eradication rates were 3/20 (15%) in patients taking erythromycin tablets and 3/19 (16%) in those taking a liquid formulation of erythromycin . All treatment regimens were well tolerated and all patients completed the prescribed course of therapy.

J Photochem Photobiol B, 1992 Dec, 16(3-4), 305 - 18
The extra-weak chemiluminescence generated during oxidation of some tetracycline antibiotics . II . Peroxidation; Michalska T et al.; This study was undertaken to establish the mechanism of chemiluminescence during the oxidation reaction of tetracycline antibiotics in the presence of molecular oxygen and H2O2 . The spectral distribution of chemiluminescence and fluorescence and the quantum yields of chemiluminescence were measured . The chemiluminescence spectrum measured with cut-off filters revealed one broad blue-green band and bands with maxima at 580, 640 and 700 nm . The bands at 580, 640 and 700 nm were similar to those observed for singlet molecular oxygen . The effect of superoxide radical, hydroxyl radical inhibitors, singlet oxygen quenchers and D2O as solvent on the light emission was also studied . The formation of singlet oxygen during the oxidation of the investigated tetracyclines was also checked using the spectrophotometric method based on the bleaching of p-nitrosodimethylaniline . A mechanism for the reactions generating electronically excited compounds is proposed.

Toxicol Appl Pharmacol, 1992 Dec, 117(2), 194 - 9
An in vitro model for assessing muscle irritation of antibiotics using rat primary cultured skeletal muscle fibers; Kato I et al.; This study examined the possibility of using rat primary cultured skeletal muscle fiber to estimate the muscle irritation of antibiotics . The cells were exposed to cefaloridine (CER), cefazolin sodium (CEZ), flomoxef sodium (FMOX), cefamandole sodium (CMD), latamoxef sodium (LMOX), or cefalotin sodium (CET) at concentrations of 0 (control), 31.25, 62.5, 125, and 250 mg/ml in culture medium for 1 hr on Day 11 of culture . Cellular creatine kinase (CK) activity was measured as an indication of cell injury . The concentration of the antibiotic, at which CK activity decreased to 50% of the control (depletion concentration 50%, DC50), was utilized as an index of cytotoxicity . DC50s of CER, CEZ, FMOX, CMD, LMOX, and CET were estimated to be 406.7, 311.1, 211.6, 132.7, 114.2, and 56.5 mg/ml, respectively . There was a good correlation between DC50 obtained in the present in vitro test and the irritation volume in the in vivo test . These results suggest that the in vitro system using rat primary cultured skeletal muscle fibers is a useful alternative model for in vivo rabbit study to evaluate muscle irritation.

Nippon Ika Daigaku Zasshi, 1992 Dec, 59(6), 450 - 6
An endoscopic study of antibiotic-associated hemorrhagic colitis; Kishida T et al.; Colonoscopy was performed on acute stage within 72 hours from onset in 48 patients with antibiotic-associated hemorrhagic colitis (AAHC) . From our observations we have developed a new endoscopic classification of AAHC and investigated the incidence of each finding in further detail . We have classified in principle the endoscopic findings of the 48 subjects into two groups: major and minor ones respectively . Category of major findings were: 1) diffuse mucosal hemorrhage (100%); 2) spotty mucosal hemorrhage (100%), and 3) linear mucosal hemorrhage (22.9%), while minor findings were: 1) irregular ulcers in 10.4%; 2) aphthoid ulcers in 6.3%, and 3) linear erosions or ulcers in 4% . Minor findings were ulcers or erosions present over the hemorrhagic mucosa associated with the moderate degree of inflammation . A histopathologic study of colon biopsy specimens from 24 patients with AAHC showed hemorrhage and inflammatory cell infiltration in the lamina propria mucosae varying from mild to moderate in extent . It was concluded that AAHC was a colonic mucosal hemorrhagic disease caused by the destruction of mucosal vessels from unknown causes and in this disease mild to moderate inflammation was partially followed by ulceration over the edematous and hemorrhagic mucosa of the colon.

Curr Opin Oncol, 1992 Dec, 4(6), 1080 - 8
Antitumor antibiotics, epipodophyllotoxins, and vinca alkaloids; Hande KR; This paper reviews manuscripts published from June 1991 to June 1992 that, in the author's opinion, have added to the understanding and clinical use of a group of commonly used antineoplastic agents . New developments highlighted include 1) clarification of the mechanism of action of the anthracyclines and epipodophyllotoxins, 2) evaluation of tests used for the early detection of bleomycin pulmonary toxicity, 3) results of studies on the epidemiology and prevention of anthracycline-induced cardiomyopathy, 4) the potential use of therapeutic drug monitoring to predict etoposide toxicity, and 5) identification of drug interactions that alter the pharmacokinetics of the epipodophyllotoxins.

Am J Gastroenterol, 1992 Dec, 87(12), 1816 - 9
Antibiotic-associated fulminant pseudomembranous colitis without toxic megacolon; Herman BE et al.; Presented is a middle-aged male who developed a fulminant case of antibiotic-associated pseudomembranous colitis characterized by leukocytosis, hypoalbuminemia, ascites, and anasarca without toxic megacolon . The patient responded slowly to medical therapy consisting of intravenous metronidazole, oral vancomycin, and parenteral nutrition . Subsequently, cholestyramine was administered . A review of the literature concerning similar cases of fulminant pseudomembranous colitis is presented.

J Bacteriol, 1992 Dec, 174(23), 7844 - 7
Multiple antibiotic susceptibility associated with inactivation of the prc gene; Seoane A et al.; A Tn5 insertion which led to increased susceptibility to multiple drugs, including tetracycline, chloramphenicol, nalidixic acid, erythromycin, spectinomycin, norfloxacin, and novobiocin, was identified in Escherichia coli . Cloning and sequence studies showed that the insertion was in the previously identified prc gene at min 40.4 . The prc product is known to function as a protease linked to processing of penicillin-binding protein 3 and lambda repressor and when absent to allow some leakage of periplasmic constituents . Complementation studies with the prc gene on plasmids showed complete recovery of parental levels of susceptibility to all drugs except chloramphenicol, with which only partial reversion to wild-type levels was observed.

J Pharm Pharmacol, 1992 Dec, 44(12), 968 - 72
Transport characteristics of cephalosporin antibiotics across intestinal brush-border membrane in man, rat and rabbit; Sugawara M et al.; The uptake of orally active cephalosporins, ceftibuten and cephradine, by intestinal brush-border membrane vesicles isolated from man, rat and rabbit was studied . In the presence of an inward H+ gradient, ceftibuten but not cephradine was taken up into intestinal brush-border membrane vesicles of man and rat against the concentration gradient (overshoot phenomenon) . In rabbit jejunal brush-border membrane vesicles, the uptake of both cephalosporins in the presence of an inward H+ gradient exhibited the overshoot phenomenon . In human and rat vesicles, the initial uptake of ceftibuten was strongly inhibited by compound V, an analogue of ceftibuten, but the uptake of cephradine was not affected by any of the cephalosporins tested, whereas in the rabbit brush-border membrane vesicles, initial uptake of both ceftibuten and cephradine were markedly inhibited by all cephalosporins and dipeptides used . These results suggest that the transport characteristics of human and rat intestinal brush-border membrane for cephalosporins are comparable, and that rabbit is an inadequate animal for investigating the transport characteristics of beta-lactam antibiotics.

Med Lab Sci, 1992 Dec, 49(4), 248 - 51
Serum creatinine assays in patients receiving the antibiotic Cefpirome (HR 810): a study of three different routine methods compared with a specific HPLC method; Legg EF et al.; Sequential timed samples were taken from patients after a single dose of a new cephalosporin--Cefpirome HR810 . The patients had been recruited in a multi-centre trial over a 12-month period . Creatinine was estimated in all of these specimens by four different techniques, embodying four different analytical principles . Interference from the drug was evident in the assay depending on the Jaffe reaction . There was also interference in the enzyme-based methods, manifested as increased imprecision due to a non-specified cause thought to be related to the age of the samples . Only the HPLC method guaranteed precise results free from drug interference.

Tijdschr Diergeneeskd, 1992 Dec 1, 117(23), 694 - 6
{Comparative clinical study of 2 antibiotic injectable preparations in the treatment of airway infections in veal calves}; Boone G et al.; The results of a comparative clinical study in which two injectable antibiotic preparations, containing enrofloxacin or neomycin-procaine penicillin were used, are reported . Four outbreaks of pneumonia in 186 calves on two farms were included in the study . Both preparations were used at a dose rate of 1 ml per 20 kg body weight for five, consecutive days . The clinical efficacy of both preparations was high (cure rates of 96 and 98%) and the clinical scores following treatment for each preparation were very much the same throughout the trial period . After the first treatment, more than 50% of the animals were considered to be healthy, after three treatments this percentage had increased to more than 80%.

Rinsho Byori, 1992 Dec, 40(12), 1275 - 80
{Effects of antibiotics on the dissociation of platelet adherence in pseudothrombocytopenia}; Sakurai S et al.; To elucidate the effects of antibiotics on platelet adherence phenomena, we examined dissociation of platelet adherence in EDTA-dependent pseudothrombocytopenia by adding Kanamycin or Colimycin . We found the rapid dissociation of platelet adherence caused by addition of Kanamycin (20 mg) or Colimycin (20 mg) in 1 ml of EDTA-anticoagulated blood from patients with EDTA-dependent pseudothrombocytopenia . This dissociation was most remarkable in the sample treated within 30 minutes after venipuncture . When the dissociation occurred, no adherent platelet was found on microscopical examinations . Complete blood cell counts and their histogram patterns after dissociation were almost same as those just after venipuncture . The dissociation occurred as soon as the antibiotics were added and remained fairly long time . The dissociation decreased in proportion to the periods of time between venipuncture and addition of antibiotics . The dissociation was caused by many other antibiotics . However, severer damage were found morphologically by adding most of them in both histogram patterns and microscopical examinations than those of aminoglycoside or peptide antibiotics.

Int J Paediatr Dent, 1992 Dec, 2(3), 139 - 43
The effect of antibiotic therapy on the oral health of cystic fibrosis children; Kinirons MJ; This study examined the relationship between antibiotic usage and plaque, gingivitis and dental caries experience in a group of children suffering from cystic fibrosis . Their scores for plaque, gingivitis and dental caries were compared with those of healthy control children who were individually matched on the basis of age, sex and social class . Significant negative relationships were noted between (i) antibiotic usage during the 4 weeks prior to examination and plaque and gingivitis scores, and (ii) antibiotic usage since the age of 6 years and DMFT . It is suggested that antibiotic therapy may be a major cause of the lower levels of dental disease observed in cystic fibrosis children.

Antibiot Khimioter, 1992 Dec, 37(12), 53 - 5
{Effect of antibiotics on the absorption of basic nutrients}; Akimova LA et al.; The impact of tetracycline, gentamicin, streptomycin, erythromycin, oxacillin, benzylpenicillin and sulfanilamides on the absorption function of the small intestine was studied in 79 patients with chronic bronchitis . The drugs were shown to mainly inhibit fat absorption: on the average, by 87 per cent in all the patients treated with tetracycline, on the average, by 89 and 36 per cent in 80-70 per cent of the patients treated with gentamicin and streptomycin, respectively, and, on the average by 26 and 16 per cent in 20-25 per cent of the patients treated with erythromycin and oxacillin, respectively . The absorption of protein decreased, on the average, by 23-74 per cent in all the patients treated with tetracycline, gentamicin and streptomycin . As for the other drugs, they had, on the average no significant effect on protein absorption . The absorption of carbohydrates (d-xylose) significantly decreased under the effect of these three drugs (by 21, 34 and 36 per cent, respectively) . The analysis revealed a relation of absorption function to the presence and degree of intestinal dysbacteriosis.

Antibiot Khimioter, 1992 Dec, 37(12), 21 - 3
{Resistance of the strain Streptomyces hygroscopicus 155 to autogenous and other antibiotics}; Moncheva PA et al.; Streptomyces hygroscopicus 155, a strain producing pandavir (nigericin) and azalomycin, was studied with respect to resistance to its own and some other antibiotics i.e . tetracycline, gentamicin, streptomycin, erythromycin, tylosin, thiostreptone, benzylpenicillin, monensin and salinomycin . An inactive variant of the culture was used in the control.

Med J Malaysia, 1992 Dec, 47(4), 273 - 9
The role of prophylactic antibiotics in caesarean section--a randomised trial; Ng NK et al.; A prospective randomised controlled study was conducted over a 6 month period on the value of administering prophylactic antibiotics in patients undergoing emergency caesarean section at the Ipoh General Hospital . A total of 222 patients were randomised to receive 24 hours of ampicillin (500 mg per dose), cefoperazone (1 gm per dose) or no antibiotics . In all parameters of patient morbidity, the group receiving cefoperazone showed significantly better results as compared to the group not receiving antibiotics . The ampicillin group also had favourable results but generally not achieving statistical significance . Prophylactic antibiotics appear to be beneficial and consideration should be given to make it a routine in all emergency caesarean sections.

Kansenshogaku Zasshi, 1992 Dec, 66(12), 1692 - 7
{A case of organizing pneumonia which had to be treated with steroids in the early phase of the disease against delayed resolution of severe pneumonia occurring even after antibiotic therapy}; Umeki S et al.; A 58-year-old male was referred to our division because of antibiotic-resistant pneumonia . A chest X-ray film revealed severe pneumonia over the left lung field but laboratory data showed no leukocytosis . Transbronchial lung biopsy findings showed the evidence consistent with organizing pneumonia . One-month prednisolone therapy produced a disappearance of the pneumonia shadow, but a giant bulla was found at the same site . It was considered that it was necessary to treat this case with a combination of effective antibiotics and steroids in the early phase of the disease.

Chem Pharm Bull (Tokyo), 1992 Dec, 40(12), 3228 - 33
Catalysis of hydrolysis and aminolysis of non-classical beta-lactam antibiotics by metal ions and metal chelates; Mendez R et al.; The Zn(2+)-tris (hydroxymethyl)aminomethane (Tris) system has a great catalytic effect on the hydrolysis and aminolysis of some beta-lactam antibiotics . In order to ascertain the mechanism of this catalysis we have analysed the effects of the beta-lactam antibiotic structure . First we studied the kinetics of the decomposition of imipenem, SCH 29482, aztreonam and nocardicin A in aqueous solution of Tris at 35.0 degrees C, 0.5 mol.dm-3 ionic strength and in the presence of metal ions (Zn2+, Cd2+, Co2+, Cu2+, Ni2+ and Mn2+) . From these studies, we conclude that Tris and metal ions (in separate solutions) exert a great catalytic effect on the hydrolysis of imipenem and SCH 29482 . We suggest that in metal ion solutions a 1:1 complex is formed between the metal ion and beta-lactam antibiotic, which is attacked by hydroxide ions . Studies of the degradation of the antibiotics studied in solutions of Tris and metal ions together indicate that the systems Cd(2+)-Tris and Zn(2+)-Tris have a great catalytic effect on the hydrolysis and aminolysis of imipenem and SCH 29482 . We suggest that this catalysis takes place via a ternary complex in which the metal ion plays a double role by (a) placing the antibiotic and the Tris in the right position for the reaction and (b) lowering the pKa of the hydroxide group of Tris, which is coordinated with the metal ion, generating a strong nucleophile.

Chem Pharm Bull (Tokyo), 1992 Dec, 40(12), 3222 - 7
Stability in aqueous solution of two monocyclic beta-lactam antibiotics: aztreonam and nocardicin A; Mendez R et al.; The catalytic effect of various buffer systems (citrates, acetates, phosphates, borates and carbonates) on the degradation of aztreonam and nocardicin A in aqueous solution was studied at 35 degrees C and a constant ionic strength of 0.5 mol.dm-3 over a pH range of 3.50 to 10.50 . The observed degradation rates, obtained by measuring the remaining intact antibiotic, were shown to follow pseudo-first-order kinetics with regard to antibiotic concentrations and to be influenced by general acid and general base catalysis . The changes in the concentration of intact beta-lactam antibiotic in the solutions were established by reverse-phase HPLC with UV-detection . In general the buffer systems employed in the kinetic studies showed a very weak catalytic effect on the degradation of aztreonam and nocardicin A . The pH-rate profiles for these antibiotics showed degradation minimums at pH 5.38 and 6.13, respectively . Aztreonam is slightly more reactive with hydrogen ions than nocardicin A and is much more reactive with hydroxide ions . In comparison with other beta-lactamic antibiotics, aztreonam and nocardicin A are much more stable in aqueous solution, except for aztreonam in a base solution, which is just as unstable as penicillins and cephalosporins . The Arrhenius activation energies were determined for aztreonam and nocardicin A at pH's 4.23, 6.59 and 8.60.

Fed Regist, 1992 Dec 11, 57(239), 58942 - 60
New drug, antibiotic, and biological drug product regulations; accelerated approval--FDA . Final rule; The 2-amino group of guanine is absolutely required for specific binding of the anti-cancer antibiotic echinomycin to DNA; Department of Pharmacology, University of Cambridge, UKThe 2-amino group of guanine is believed to be a critical determinant of potential DNA binding sites for echinomycin and related quinoxaline antibiotics . In order to probe its importance directly we have studied the interaction between echinomycin and DNA species in which guanine N(2) is deleted by virtue of substitution of inosine for guanosine residues . The polymerase chain reaction was used to prepare inosine-substituted DNA . Binding of echinomycin, assessed by DNAse I footprinting, was practically abolished by incorporation of inosine into one or both strands of DNA . We conclude that both the purines in the preferred CpG binding site need to bear a 2-amino group to interact with echinomycin.

Ital J Gastroenterol, 1992 Nov-Dec, 24(9 Suppl 2), 2 - 3
Requirements for the use of intestinal action antibiotics in the treatment of ulcerative colitis; Campieri M et al.; The causes of ulcerative colitis are still unknown and above all the circumstances which can lead to inflammatory episodes are unclear . Antibiotic therapy has not provided encouraging results so far but it is possible that the pathogenesis of this disease may involve bacterial species which have not yet been identified . The use of an antibiotic with specific colic activity therefore seems to be justified.

J Nat Prod, 1992 Nov, 55(11), 1638 - 42
5-Epi-isospongiaquinone, a new sesquiterpene/quinone antibiotic from an Australian marine sponge, Spongia hispida; Urban S et al.; An Australian marine sponge, Spongia hispida, has been found to contain a new sesquiterpene/quinone identified by detailed spectroscopic analysis and chemical derivatization as the antibiotic 5-epi-isospongiaquinone {3} . The complete stereostructure for 3 was determined by detailed spectroscopic analysis and chemical correlation with the known marine natural product isospongiaquinone {2} . Co-occurring with 3 was an ethylated analogue, 5-epi-homoisospongiaquinone {4}, which was speculated to be an artifact of the isolation process . A revised structure 15 for the known marine metabolite, smenorthoquinone {13}, is also presented.

Equine Vet J, 1992 Nov, 24(6), 443 - 9
Open drainage, intra-articular and systemic antibiotics in the treatment of septic arthritis/tenosynovitis in horses; Schneider RK et al.; Open drainage was used to treat 26 horses with persistent or severe septic arthritis/tenosynovitis . Infected synovial structures were drained through a small (3 cm) arthrotomy incision that was left open and protected by a sterile bandage . Joint lavage was performed in all 26 horses . In addition to systemic antibiotics, 23 of these horses were also treated with intra-articular antibiotics; amikacin (17 horses), gentamycin (2 horses), cefazolin (2 horses), and 2 horses were injected at different times with gentamycin and amikacin . The infection was eliminated from the involved synovial structures in 25 of 26 horses; 24 survived and were released from the hospital . The arthrotomy incisions healed by granulation in 16 horses; in 9 horses the arthrotomy incision was sutured closed once the infection was eliminated . Seventeen horses returned to soundness and resumed athletic function . Open drainage was an effective method of achieving chronic drainage from a joint or tendon sheath . It is indicated in horses that have established intra-synovial infections or in horses that do not respond to joint lavage through needles.

Kokyu To Junkan, 1992 Nov, 40(11), 1105 - 8
{Prophylactic use of antibiotics for fever following fiberoptic bronchoscopy and bronchography}; Saka H et al.; To evaluate the effect of bacampicillin hydrochloride on fever following fiberoptic bronchoscopy and bronchography, we conducted multi-institutional randomized study . In bronchographic examinations, the rise of body temperatures in the bacampicillin group (0.82 +/- 0.13 degrees C: mean +/- SE) was significantly smaller than that in the control group (1.39 +/- 0.25 degrees C) on the second day of examination . Bacterial infection may contribute to the rise of temperature on the day following bronchography, but no pneumonia or sepsis was observed . There was no differences in the rise of body temperature on the first, third or fourth day . In fiberoptic bronchoscopic examinations, there was no difference between the two groups . We conclude that there is no clinical indication of the value of prophylactic use of antibiotics in either fiberoptic bronchoscopy or bronchography.

Int J Pediatr Otorhinolaryngol, 1992 Nov, 24(3), 245 - 51
Otolaryngology and infectious disease team approach for outpatient management of serious pediatric infections requiring parenteral antibiotic therapy; Einhorn M et al.; Children with community-acquired serious otolaryngologic infections are conventionally hospitalized for parenteral antibiotic therapy . However, effective and safe outpatient therapy is desirable since it is less traumatic and less costly . During a 24-month period outpatient parenteral antibiotic therapy, usually once daily i.m . ceftriaxone, was evaluated in 41 children with serious otolaryngologic infections (acute mastoiditis, complicated otitis media, severe external otitis and severe sinusitis with orbital or periorbital involvement) . Daily visits and compliant capable parents were considered essential for outpatient management . Diagnosis, plan for management and daily follow-up evaluations were carried out in cooperation by otolaryngology and infectious disease specialists . Nineteen children (45%) were treated initially in the hospital and 22 children (55%) were treated entirely as outpatients . The mean duration of outpatient treatment, using once daily i.m . ceftriaxone was 5.7 days (range 1-13) . The overall clinical cure rate was 98% and no serious side effects were observed . One case of sinusitis-orbital cellulitis relapsed during therapy . Most patients and parents returned to normal life activities within 72 h from starting outpatient therapy . Our data suggest that many children with serious otolaryngologic infections can be managed successfully and safely as outpatients by a combined team of otolaryngology and infectious disease specialists.

Clin Orthop, 1992 Nov, (284), 303 - 9
In vitro elution characteristics of commercially and noncommercially prepared antibiotic PMMA beads; Nelson CL et al.; The successful treatment of osteomyelitis with commercially prepared gentamicin-polymethylmethacrylate (PMMA) (Septopal) beads and surgical debridement has led to the use of this technique in the United States . However, commercially prepared gentamicin-PMMA beads are not currently available to orthopedic surgeons in the United States . Therefore, these surgeons commonly manufacture their own antibiotic-containing cement beads in the operating room at the time of surgery . There is little data that compare the antibiotic elution characteristics of such preparations to commercially prepared gentamicin-PMMA beads . This study compares the measured amount of antibiotic elution of either gentamicin or tobramycin from laboratory manufactured Zimmer, Simplex, or Palacos beads to commercially prepared gentamicin-PMMA (Septopal) beads . During a 30-day study period, commercially prepared gentamicin-PMMA beads eluted more total antibiotic and maintain higher concentrations than did antibiotic acrylic composites manufactured in the authors' laboratory.

Biosci Biotechnol Biochem, 1992 Nov, 56(11), 1776 - 9
Uncoupling action of antibiotic sporaviridins with rat-liver mitochondria; Miyoshi H et al.; The effects of the glycoside antibiotic sporaviridins (SVDs) on oxidative phosphorylation of rat-liver mitochondria were examined . SVDs released state 4 respiration, dissipated transmembrane electrical potential, and accelerated ATPase activity . These facts demonstrated that SVDs are potent uncouplers of oxidative phosphorylation . During the uncoupling caused by SVDs, large amplitude swelling and oxidation of intramitochondrial NAD(P)H occurred, suggesting that SVDs greatly enhanced nonspecific permeability of the inner mitochondrial membrane . It is suggested that the uncoupling action of SVDs might be caused by dissipation of proton electrochemical potential due to an increase in the permeability of inner mitochondrial membrane.

Antibiot Khimioter, 1992 Nov, 37(11), 32 - 5
{Comparative study of the therapeutic effect of the glycopeptide antibiotics eremomycin, vancomycin and ristomycin in a model of antibiotic-associated colitis in golden hamsters}; Rukhlina AA; Experiments with a model of intraperitoneal or intragastric lincomycin-induced fatal colitis indicated that eremomycin, vancomycin and ristomycin administered orally in daily doses of 100, 100 and 200 mg/kg, respectively, for 5 days protected the animals from development of antibiotic-associated colitis (AAC), which was evident from prolongation of their life-span to 10-23 days against 3-9 days in the controls . Eremomycin administered intraperitoneally according to an analogous scheme protected the animals from development of AAC, prevented 45 per cent of the animals from death and prolonged the life-span of the other animals to 15-28 days against 3-9 days in the controls . Vancomycin administered intraperitoneally was somewhat more efficient . Still, unlike eremomycin it had a local irritating effect . The protective effect of ristomycin administered intraperitoneally was much lower than that of vancomycin and eremomycin.

Ital J Gastroenterol, 1992 Nov-Dec, 24(9 Suppl 2), 19 - 22
Non-absorbable antibiotics in the treatment of diverticular disease of the colon; Papi C et al.; Diverticular disease of the colon is a common health problem in western societies . Most patients with colonic diverticula are asymptomatic; it has been estimated that only 20% of individuals harboring diverticula will develop symptoms and signs of illness and a minority will develop major complications . Medical treatment of diverticular disease is aimed to the relief of symptoms and to prevent inflammatory complications . High fiber diets and antispasmodics are widely used in the treatment of uncomplicated diverticular disease although their real efficacy has not been fully elucidated . Antibiotics are used to treat major inflammatory complications of diverticular disease but apparently there is no rationale for their use in uncomplicated disease where an inflammatory component is, by definition, excluded . However two recent papers suggest a possible role of rifaximin, a broad-spectrum poorly absorbable antibiotic, in the management of mild acute diverticulitis and in obtaining symptomatic relief in patients with uncomplicated disease . Prospective studies with an adequate sample size per group of treatment are needed to assess the efficacy of cyclic long term administration of poorly absorbable antibiotics in preventing major complications of diverticular disease.

Zhonghua Wai Ke Za Zhi, 1992 Nov, 30(11), 682 - 3, 700
{Sensitivity of Staph aureus and Ps . aeruginosa and clinical application of antibiotics in patients with burn septicemia}; Zhang H; The sensitivity of 245 strains of Staph . aureus and 171 strains of Ps . aeruginosa to antibiotics was tested in patients with burn septicemia . The results indicated that both the bacteria were resistant to the widely used antibiotics . The causes for producing the resistance to drugs were analyzed . We consider that "circular therapy" of antibiotics, alternatively stopping and reusing some antibiotics according to the variation in the bacterial resistance to drugs, should be a valuable method for preventing the resistance to drugs.

Antibiot Khimioter, 1992 Nov, 37(11), 40 - 3
{Antibiotic therapy in children with pertussis}; Petrova MS et al.; The data accumulated within the last years required revision of the indications to the use of antibiotics in treatment of pertussis . One of the aims of antibiotic therapy in pertussis was to prevent colonization of B . pertussis in the respiratory tracts . With that end in view the choice of antibiotics should be limited by those, to which the pathogen is the most sensitive i.e . erythromycin, ampicillin and augmentin . Comparative efficacy of erythromycin and ampicillin during the first 2 weeks of the disease was studied in 79 infants at the age not older than 1 year with pertussis and it was shown that erythromycin was advantageous by its therapeutic activity and less side effects . Expedience of the antibiotic therapy during the spastic period for providing a preventive effect on development of bronchopulmonary complications was studied in 201 patients with pertussis . No preventive effect of the antibiotics on development of the bronchopulmonary complications defined by the secondary bacterial flora was recorded . In the group of the patients treated with the antibiotics prophylactically (group 1) the complications were 2.6 times more frequent than in the patients treated with pathogenetic agents alone (group 2) . Intrahospital pneumonia developed in 8.9 per cent of the patients in group 1 and in 1.5 per cent of the patients in group 2 . Therefore, antibiotics should not be used at the late periods of pertussis for prophylaxis of secondary bacterial complications.

Pediatr Med Chir, 1992 Nov-Dec, 14(6), 565 - 9
{Allergy to beta-lactam antibiotics in childhood . Diagnostic problems}; Venuti A et al.; This study reports about 126 children with an age ranging from 12 months to 12 years having RA to beta-lactamase . More children with an age ranging from 7-12 years (59.5%), and more male (65.9%) than female subjects were studied . 76 patients (60.3%) showed a familial anamnesis of allergic diseases or similar diseases and a personal anamnesis of allergic diseases (45.2%) . Among the RA responsible substances the more frequent were semisynthetic penicillin (44.6%) followed by cephalosporin and penicillin . Most clinical manifestations (87.3%) were cutaneous reactions and in smaller number of cases it was possible to observe gastroenteric or respiratory reactions . In 121 patients cutaneous tests were undertaken (Prick tests and intradermoreactions), patch tests, employing: PPL, MDM, Penicillin, Ampicillin, Cephaloridine . 5.8% of the studied subjects showed an allergy . Particularly 2.4% showed a "early" positivity . RAST was carried out in 92 patients and 3 of them showed a positive result (3.2%) . This study stresses the opportunity to carry out allergologic tests within 6 months since the beginning of RA . In fact especially in children this test result can soon become negative . Furthermore the reduced percentage of positive allergologic tests can be due to the inclusion in other studies of patients with "coincidental reactions" . A certain number of RA can be caused by additive to "per os" products . Finally it will be possible to use "tests dose" even in selectioned cases . These tests can frequently exclude the etiopathogenetic responsibility of beta-lactamic substances.

Lik Sprava, 1992 Nov-Dec, (11-12), 119 - 22
{The structural bases of the cardiotoxic action of the anti-tumor antibiotic carminomycin}; Ishchenko VE et al.; The authors substantiate morphological and structural-functional basis of the cardiotoxic effect of the antitumor anthracycline antibiotic carminomycin after its single intraperitoneal administration in maximum tolerable doses . Results indicate that the cause of development of cardiac failure after administration of carminomycin to experimental animals in the development of an alternative and plastic cardiac failure prevalence of type I.

J Cardiovasc Surg (Torino), 1992 Nov-Dec, 33(6), 660 - 3
Intralymphatic antibiotic delivery for reducing acute prosthetic graft infection; Folsom DL et al.; The lymphatic system has been implicated as a source of synthetic graft contamination when grafts are implanted in the presence of a distal septic focus . In previous studies, radical lymphatic excision and ligation were shown to reduce acute graft sepsis . However significant lymphedema precluded its clinical application . The present study was undertaken to evaluate methods for reducing acute graft sepsis while avoiding lymphatic obstructive complications . Twenty dogs were divided into one control and two experimental cohorts . Femoral interposition grafts were placed in each dog . A hind paw septic focus was introduced and therapy included a control (Group I--no therapy), intravenous antibiotics in Group II and intralymphatic antibiotics in Group III . Graft, blood and tissue cultures from each dog were taken at 48 hours . Lymphatic antibiotic therapy resulted in significantly improved graft culture results when compared to the control (p = 0.0003) and intravenously treated animals (p = 0.007) . Blood cultures in the intralymphatically treated group were also significantly better (p = 0.003) than the control group.

J Chromatogr, 1992 Oct 30, 624(1-2), 153 - 70
Chromatographic analysis of antibiotic materials in food; Bobbitt DR et al.; The monitoring of food materials for antibiotic residues is an area of increasing concern and importance due to the potential impact on human health . Large-scale screening applications require methods that are rapid, accurate, provide low detection limits and are free from interference . The problem is further complicated by the wide range of chemical functionalities and modes of operation exhibited by the antibiotic materials of physiological significance in use today . As demonstrated, chromatographic methods provide many of the advantages necessary for screening applications . Judicious choice of sample preparation method, separation mode and detection strategy can provide significant immunity from problems associated with the food matrix . Gas chromatography can provide extremely high separation efficiencies, however, only a limited number of antibiotic compounds are inherently volatile enough for direct analysis by gas chromatography . Derivatization to enhance the volatility of the antibiotic is one approach to overcome this limitation . Among the methods available, reversed-phase high-performance liquid chromatography is used extensively for the analysis of many antibiotic systems as it does not require derivatization and it combines relatively high separation efficiencies with low detection limits . The diverse group of properties exhibited by the antibiotic materials in use today suggests that the choice of detection strategy is a key component in the successful development of an analysis technique . Derivatization of the antibiotic material is frequently used to add either a fluorogenic of chromogenic moiety to the antibiotic compound to enhance detection . Derivatization procedures suffer from several limitations which are problematic when making measurements in complicated food matrices . Among the different detection modes utilized for antibiotic analysis, polarimetric detection has the potential to provide extremely selective detection of most antibiotic materials, and this selective response can minimize many of the constraints placed upon the separation system by the sample matrix . Although many of the separation modes used for antibiotic analysis are well developed, separations based on capillary electrophoretic methods have much potential in the field of antibiotic analysis . Future investigations are needed to extend the generality of these techniques and expand their use into the field of food analysis.

Neurosci Lett, 1992 Oct 12, 145(2), 189 - 92
Centrally administered aminoglycoside antibiotics antagonize naloxone-precipitated withdrawal in mice acutely dependent on morphine; Robles I et al.; The effects of i.c.v . administration of several aminoglycoside antibiotics on naloxone-precipitated morphine withdrawal symptoms were evaluated in mice acutely dependent on morphine . Neomycin (10-40 micrograms/mouse), gentamicin (40-160 micrograms/mouse) and kanamycin (80-320 micrograms/mouse) produced a dose-dependent reduction of the number of precipitated jumps, forepaw tremors and head shakes . The order of potency of the aminoglycoside antibiotics on all withdrawal symptoms was neomycin > gentamicin > kanamycin, which is the same order that these drugs show as N-type calcium channel blockers . The capacity of several drugs that decrease neuronal calcium availability (such as lanthanum and L-type calcium channel blockers) to antagonize opiate withdrawal is well known . In the light of these findings, our results suggest that the mechanism of aminoglycoside-induced inhibition of morphine abstinence may be related to the capacity of these antibiotics to block N-type calcium channels, and to decrease neuronal calcium availability.

J Chromatogr, 1992 Oct 9, 623(1), 153 - 8
Determination of tetracycline antibiotics by reversed-phase high-performance liquid chromatography with fluorescence detection; Iwaki K et al.; A highly sensitive method for the determination of tetracycline antibiotics (TCs) using reversed-phase high-performance liquid chromatography with fluorescence detection is presented . This method was based on the use of disodium ethylenediaminetetraacetate (EDTA) and calcium chloride as fluorescence-increasing reagents in the mobile phase . The concentrations of each reagent in the mobile phase greatly influenced the fluorescence intensity of TCs . When the concentration of EDTA and calcium chloride were 25 and 35 mM, respectively, and the pH of the mobile phase was 6.5, the maximum fluorescence intensity was obtained . The column temperature hardly influenced the fluorescence intensity . At 3.75 ng of TCs injected, the precision (relative standard deviation) ranged from 1.12 to 2.20% . In the range 0.075-37.5 ng for tetracycline and oxytetracycline and 0.225-37.5 ng for chlortetracycline, a linear response was observed . The detection limits of this method were 49-190 pg for three different TCs . The proposed method was applied to the determination of one of the TCs in pharmaceuticals by the internal standard method using other TCs as internal standards and was also applied to determination of TCs added to fish tissue.

Lik Sprava, 1992 Oct, (10), 57 - 60
{The morphological aspects of the protective action of enterosorbent K(2)9 during the use of the antitumor anthracycline antibiotic carminomycin}; Ishchenko VE et al.; The authors substantiate morphologically the protector effect of K(2)9 enterosorbent during its parallel use with the antitumour anthracyclin antibiotic carminomycin . The agent was administered intraperitoneally in animals at the maximum tolerable dose . Use of the K(2)9 enterosorbent reduces the cardiotoxic effect of carminomycin.

J Antibiot (Tokyo), 1992 Oct, 45(10), 1609 - 17
Production of new anthracycline antibiotics 1-hydroxy-oxaunomycin and 6-deoxyoxaunomycin by limited biosynthetic conversion using a daunorubicin-negative mutant; Yoshimoto A et al.; A limited biosynthetic conversion of some known anthracyclinones using a specific daunorubicin-nonproducing mutant provided four new anthracycline antibiotics: 1-Hydroxy-10-methoxycarbonyl-13-deoxocarminomycin; 1-hydroxy-13-deoxocarminomycin; 1-hydroxyoxaunomycin and 6-deoxyoxaunomycin . Their isolation and purification from bioconversion broth, structural determination and antitumor activities against leukemic L1210 cells are described.

Antimicrob Agents Chemother, 1992 Oct, 36(10), 2322 - 7
Use of Tn5lac to study expression of genes required for production of the antibiotic TA; Tolchinsky S et al.; The beta-galactosidase activities arising from Tn5lac insertions in several genes required for antibiotic TA production were measured under different growth conditions . In all of the non-TA-producing mutants, the beta-galactosidase specific activity was higher when the cells were grown in nutrient-limited 0.5CTS medium (0.5% Casitone plus alanine, serine, and glucose) than in rich 2CT medium (2% Casitone) . One of the mutants, 420, had low beta-galactosidase specific activity in both media . The other seven mutants containing inserts in genes essential for TA production had specific activities of 139 to 367 U/mg of protein in 0.5CTS medium and 11 to 48 U/mg of protein in 2CT medium . The beta-galactosidase specific activities of two strains, 1030 and 420, increased during exponential growth in 0.5CTS medium . The beta-galactosidase specific activities of both strains increased greatly when the cells were grown in the presence of magnesium phosphate, which traps ammonium ions . The Tn5lac insertions in 1030 and 420 were used to screen for mutants with increased levels of transcription . An N-methyl-N'-nitro-N-nitrosoguanidine-induced mutation in 1030 that mapped 17 kb from the omega 1010 insert increased the specific activity of beta-galactosidase 21 times in 2CT medium . The regulatory mutation appears to release the repression caused by 2CT medium . A UV-induced mutation in 420 increased the beta-galactosidase specific activity 1.4 to 2.4 times . Medium conditions that affect the transcription of TA genes are discussed in terms of enhanced antibiotic TA production.

Am J Hosp Pharm, 1992 Oct, 49(10), 2469 - 74
Antibiotic-impregnated cement use in U.S . hospitals; Fish DN et al.; The results of a survey of the use of antibiotic-impregnated bone cement and cement beads in U.S . hospitals are reported . A random sample of hospitals was selected from all hospitals registered with the American Hospital Association . A questionnaire designed to characterize the extent of use of the products and the degree of pharmacy involvement was mailed to the pharmacy directors at 547 hospitals nationwide . The response rate was 61.7% (336 evaluable returns) . Ninety hospitals (26.9%) reported using antibiotic-impregnated bone cement or cement beads . Product use was significantly greater in urban hospitals, hospitals larger than 200 beds, teaching hospitals, and hospitals with pharmaceutical services in the operating rooms . Most facilities using the products were community hospitals . Total hip arthroplasty, total knee arthroplasty, and chronic osteomyelitis were the most common indications for use . Systemic antibiotics were also administered in the great majority of hospitals reporting use of the products . The products were generally used in fewer than one procedure per month . Aminoglycosides and various cephalosporins were the antibiotics most commonly used; most have not been adequately studied for this use . Although nearly all the hospital pharmacies purchased antibiotics for these products, none mixed cement and only two premanufactured antibiotic beads . About one fourth of the hospitals surveyed reported using antibiotic-impregnated bone cement and cement beads, although the total number of patients being treated was small.

Ann Pharmacother, 1992 Oct, 26(10), 1292 - 5
Antibiotic use in urban whites and blacks: the Minnesota Heart Survey; Melnick SL et al.; OBJECTIVE: To assess racial differences in the use of antibiotics, including penicillins, erythromycins, tetracyclines, sulfas, and cephalosporins . DESIGN: Population-based surveys, conducted from 1985 to 1987 . SETTING: The seven-county metropolitan area of Minneapolis-St . Paul, MN . PARTICIPANTS: 3127 whites (response rate 68 percent) and 1047 blacks (response rate 65 percent), aged 35-74 years . RESULTS: White women (26 percent of 1625) were more likely to report having taken an antibiotic in the past year than were white men (18 percent of 1502), black women (18 percent of 590), or black men (15 percent of 457) . Reported antibiotic usage decreased with increasing age . Black men were more likely than white men to report the use of tetracyclines or sulfas; otherwise, white men reported higher usage prevalences . White women reported higher usage prevalences of all drug classes than black women . CONCLUSIONS: Significant independent predictors of antibiotic use were younger age, white race, and female gender . Potential explanations for these differences include differences in patient access, physician-prescribing behaviors, or both.

Surgery, 1992 Oct, 112(4), 788 - 94; discussion 794-5
Duration of antibiotic therapy for penetrating abdominal trauma: a prospective trial; Fabian TC et al.; BACKGROUND . The optimal duration of antibiotic use in penetrating abdominal trauma is incompletely defined . It is generally accepted that short-term antibiotics are appropriate for low-risk wounds . However, with colon injury and significant degree of injury, abdominal trauma index (ATI) more than 25, concern exists that short-term treatment is not adequate . METHODS . The study was a prospective double-blind trial of 24-hour treatment (cefoxitin or cefotetan) compared with 5-day treatment in 515 patients . Major abdominal infections (MAI) included abscess, necrotizing fasciitis, and diffuse peritonitis . RESULTS . MAI occurred in 8% of those patients with 1-day therapy and 10% with 5-day therapy . Subgroup analysis of high-risk groups (colon wounds and ATI of more than 25) showed the following MAI rates: colon, 1-day therapy, 14%; 5-day therapy, 15%; ATI of more than 25, 1-day therapy, 17%; 5-day therapy, 30% . CONCLUSIONS . Regardless of contamination and degree of injury, 24-hour antibiotic therapy is satisfactory for all penetrating abdominal trauma.

J Microencapsul, 1992 Oct-Dec, 9(4), 469 - 80
Polyacrylate resin microcapsules for taste masking of antibiotics; Friend DR; Various microencapsulated dosage forms were prepared to limit the release of an antibiotic in solution for up to 3 days and in the oral cavity following per oral administration . An experimental antibiotic, clarithromycin (TE-031), was used in these studies . The drug was first encapsulated in gelatin followed in some cases by crosslinking with glutaraldehyde . The gelatin microcapsules were then coated with acrylic resins (Eudragit), whose solubility properties vary according to pH . A non-solvent coacervation technique was used to apply the Eudragit resins . It was found that crosslinking the gelatin retarded release of TE-031 somewhat relative to that from uncrosslinked gelatin microcapsules in a 72h release experiment conducted at room temperature . Coating the gelatin microcapsules with Eudragit resins L100, S100, or E100 slowed the release of TE-031 further still; less TE-031 was released over 72 h from the Eudragit-coated formulations prepared with crosslinked gelatin compared with formulations prepared with uncrosslinked gelatin . The Eudragit E100-coated crosslinked gelatin microcapsule formulation was most effective in preventing release of the TE-031 under simulated conditions of storage in an aqueous solution.

Biosci Biotechnol Biochem, 1992 Oct, 56(10), 1592 - 5
Cloning and nucleotide sequencing of the antitumor antibiotic C-1027 apoprotein gene; Sakata N et al.; The apoprotein gene for a chromoprotein antitumor antibiotic, C-1027, was cloned from the producer strain, Streptomyces globisporus C-1027, and sequenced . The process verified that; (1) the sequence included the entire structural gene directing a precursor of the apoprotein (pre-apoprotein having Met1---Ala33 leader peptide ahead of the apoprotein) and flanking regions, (2) the amino acid sequence of the apoprotein deduced from the base sequence perfectly matched the one based on protein analysis, (3) 3rd letters of the codons were 88% G or C, while the 1st plus the 2nd letters were 63% G or C, (4) the structural gene had 57% homology with that of macromomycin apoprotein (mcmA) while the flanking regions had little homology with the corresponding ones of mcmA, except some homology at the -10th and -35th promoter regions, and (5) the gene was transcribed as a monocistronic mRNA in an early growth phase, independent of chromophore production.

Antimicrob Agents Chemother, 1992 Oct, 36(10), 2316 - 21
Mutation and mapping of genes involved in production of the antibiotic TA in Myxococcus xanthus; Varon M et al.; Transposition of TnV and Tn5lac into Myxococcus xanthus yielded 8,381 kanamycin-resistant mutants that were tested for antibiotic TA production . Twenty-four of the mutants were nonproducers of TA (less than 0.4 ng/ml), and 3 produced a higher level (2.5 micrograms/ml) than the parent strain (1.5 micrograms/ml) . For most of the strains, there was 100% cotransduction between kanamycin resistance and the altered TA phenotype . Southern blot analysis of restriction digests of the mutant DNA indicated that the transposons were inserted at different sites on the M . xanthus chromosome . The TA genes were mapped by cotransduction between pairs of mutants following replacement of the initial insert of one of the pair with the tetracycline resistance transposon Tn5-132 . Nine of the 13 nonproducers tested were linked over a 36-kb stretch of the chromosome . There was no linkage between one of the overproducers and any of the nonproducers tested.

FEMS Microbiol Lett, 1992 Oct 1, 76(1-2), 89 - 94
Purification and characterization of macrolide 2'-phosphotransferase type II from a strain of Escherichia coli highly resistant to macrolide antibiotics; Kono M et al.; The resistance mechanism of Escherichia coli BM2506 to macrolides was found to be due to inactivation . Inactivated oleandomycin was identified as oleandomycin 2'-phosphate by thin-layer chromatography . A new type of macrolide-phosphorylating enzyme, macrolide 2'-phosphotransferase type II (MPH(2')II), was detected, purified 95-fold and its enzymological properties investigated . MPH(2')II was a constitutive intracellular enzyme which showed high levels of activity with both 14-member-ring and 16-member-ring macrolides . The optimum pH for the inactivation of oleandomycin was 8.2 and the optimum temperature of the reaction was 40 degrees C . Enzyme activity was lost by heat treatment at 60 degrees C for 1 min . The isoelectric point and M(r) of the enzyme were 5.3 and 48,000, respectively . Purine nucleotides, such as ITP, GTP and ATP, were effective as cofactors in the inactivation of macrolides . An inhibitory effect of iodine, EDTA, or divalent cations on MPH(2')II activity was observed.

Bioorg Khim, 1992 Oct-Nov, 18(10-11), 1341 - 60
Molecular structure and mechanisms of action of cyclic and linear ion transport antibiotics; Duax WL et al.; As a direct result of the vision, determination, and magnetic personality of Yuri Ovchinnikov a collaboration between the Shemyakin Institute of Bioorganic Chemistry and the Medical Foundation of Buffalo was begun in the early 1970's . The collaboration generated valuable insight into the structural basis for the capture, transport, and release of ions by ion transport antibiotics and the basis for the ion selectivity of these compounds . The collaboration produced dozens of joint publications on the structure and function of cyclic and linear ion transport antibiotics, fostered fruitful exchange visits between scientists in the two Research Institutes and has been a major source of creativity in my scientific career and those of many of my colleagues in Buffalo . This review summarizes major accomplishments of the collaboration.

Lancet, 1992 Sep 26, 340(8822), 767 - 70
Simplification of antibiotic dose adjustments in renal insufficiency: the DREM system; Maderazo EG et al.; Many clinicians, unassisted by reference books, are unable to make the required dose adjustment of antibiotics needed when a patient has renal insufficiency . We describe the DREM (dosing in renopathy by easy-to-use multipliers) system, which simplifies the understanding and the process of dose adjustment . DREM is a two-step process: Cockcroft and Gault estimation of creatinine clearance (CLcr) from age, sex, and serum creatinine and calculation of the adjusted dose or dosing interval by multipliers . If the normal dose is multiplied by the dose multiplier (CLcr/100) and the dosing interval by the interval multiplier (100/CLcr), the adjusted dose and interval, respectively, are obtained . Theoretical trough concentrations calculated with the DREM system correlated closely (r = 0.9) with actual concentrations obtained from doses calculated by the Hull and Sarubbi method in 23 patients . With DREM, gentamicin or tobramycin trough concentrations above 2 micrograms/ml were less likely to occur . The DREM system is a simple and easily remembered method for dose adjustments of certain anti-infective agents in renal insufficiency . Dose estimates with this method are reasonably accurate and compare favourably with other standard methods of correction.

J Biol Chem, 1992 Sep 25, 267(27), 19117 - 22
Use of 50 S-binding antibiotics to characterize the ribosomal site to which peptidyl-tRNA is bound; Odom OW et al.; Five antibiotics (puromycin, erythromycin, lincomycin, sparsomycin, and virginiamycin M1) that bind specifically to the 50 S ribosomal subunit near the peptidyl transferase center were used to compare and characterize the positions of bound AcylPhe-tRNA in the puromycin-reactive and -unreactive states . Binding of the antibiotics was quantitatively measured by their perturbation of fluorescence from probes attached to the alpha-amino group of Phe-tRNA . Derivatives of three probes with differing chemical characteristics and environmental sensitivities were used: a coumarin, an aminonaphthalenesulfonate, and a pyrene . The effects of the antibiotics on the fluorescence of labeled AcylPhe-tRNAs in the two states, while generally qualitatively similar, are nonetheless quantitatively distinct, as are the calculated binding constants for the antibiotics . Puromycin, as reported earlier, binds to both the puromycin-reactive and -unreactive states, but its dissociation constant is higher for the latter state . Erythromycin binds tightly to ribosomes bearing labeled AcylPhe-tRNA in either the puromycin-reactive or -unreactive state . Its effect on the fluorescence of the labeled tRNA is very similar in the two states, except with the pyrene probe, where it has a larger effect in the puromycin-reactive state . Lincomycin and sparsomycin bind to both ribosomal states, but both bind more tightly to the puromycin-reactive state, the extent of the difference varying with the identity of the fluorescent probe . Virginiamycin M1 binds to ribosomes with AcylPhe-tRNA in the puromycin-reactive site, but its binding could not be detected to ribosomes with AcylPhe-tRNA in the puromycin-unreactive site.

Nucleic Acids Res, 1992 Sep 25, 20(18), 4717 - 20
Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli 23S ribosomal RNA; Douthwaite S; Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli ribosomes has been compared by chemical footprinting . The protection afforded by both drugs is limited to the peptidyl transferase loop of 23S rRNA . Under conditions of stoichiometric binding at 1 mM drug concentration in vitro, both drugs strongly protect 23S rRNA bases A2058 and A2451 from dimethyl sulphate and G2505 from kethoxal modification; G2061 is also weakly protected from kethoxal . The modification patterns differ in that A2059 is additionally protected by clindamycin but not by lincomycin . The affinity of the two drugs for the ribosome, estimated by footprinting, is approximately the same, giving Kdiss values of 5 microM for lincomycin and 8 microM for clindamycin . The results show that in vitro the drugs are equally potent in blocking their ribosomal target site . Their inhibitory effects on peptide bond formation could, however, be subtly different.

Cancer Lett, 1992 Sep 14, 66(1), 29 - 34
Increased survival of L1210 leukemic mice by prevention of the utilization of extracellular polyamines . Studies using a polyamine-uptake mutant, antibiotics and a polyamine-deficient diet; Ask A et al.; When L1210 leukemia cells are inhibited in their polyamine synthesis by treatment with alpha-difluoromethylornithine (DFMO), their growth in culture is strongly suppressed . In striking contrast, the survival of L1210 leukemic mice is only marginally prolonged by DFMO treatment . This inconsistency is due to the fact, that in the mouse the tumor cells can utilize extracellular polyamines to compensate for the decrease in putrescine and spermidine synthesis caused by DFMO treatment . In the present study, we demonstrate that a reduction in the transport of polyamines into the tumor cells is a more effective means of increasing the therapeutic effect of DFMO than is a reduction in the supply of extracellular polyamines . DFMO treatment cured 30-75% of leukemic mice bearing mutant L1210-MGBGr cells deficient in polyamine uptake, but only slightly increased the survival time of leukemic mice bearing the parental L1210 cells despite the fact that the supply of extracellular polyamines was reduced (by feeding the mice a polyamine-deficient diet containing antibiotics) . The effectiveness by which DFMO cured leukemic mice bearing L1210-MGBGr cells appeared to be sex dependent . Thus, 58% of the female mice, as compared to 30% of the male mice, were cured by DFMO treatment.

Gene, 1992 Sep 1, 118(1), 127 - 9
Cloning and sequence of a gene encoding the L7/L12 ribosomal protein equivalent of Streptomyces antibioticus; Parra F et al.; A 50S ribosomal(r) protein from the vegetative mycelium of Streptomyces antibioticus, that is absent or modified in the spore 50S r-subunit, was purified by HPLC . Determination of its N terminus and comparison with amino acid sequence data bases indicated a strong homology with the L7/L12 r-protein from Streptomyces griseus . Screening of a cosmid library of S . antibioticus chromosomal DNA with a 20-mer oligodeoxyribonucleotide probe, corresponding to an internal region of the N terminus, allowed the isolation of two hybridizing clones . A 0.90-kb HindIII-BamHI fragment from one of these clones was sequenced and found to contain a 387-bp open reading frame . The deduced gene product shows clear homology with L7/L12 r-protein equivalent from different bacteria.

Ophthalmic Surg, 1992 Sep, 23(9), 622 - 4
The pH of antibiotic vitreous infusion combinations: a potential cause of retinal toxicity; Winkler BS et al.; Experiments were undertaken to measure the pH of solutions of commonly used intravitreal antibiotics in various irrigating solutions to determine whether a change in pH might be a factor in antibiotic-induced retinal toxicity . Such retinal toxicity has been particularly damaging when solutions of gentamicin have been used . The pHs of the following solutions were measured: gentamicin, amikacin, methicillin, tobramycin, and vancomycin, combined with balanced salt solution (BSS) PLUS (bicarbonate buffer), BSS (citrate/acetate buffer), and lactated Ringer's solution (lactate buffer) . Each of these antibiotics induced a concentration-dependent decrease in pH of the solutions; gentamicin, amikacin and tobramycin produced the largest shifts . The results also demonstrated that BSS PLUS acts as the strongest buffer and lactated Ringer's as the weakest . We conclude that it is important to determine the pH of intraocular antibiotic irrigating solutions, not just the pH of the antibiotics.

J Dermatol, 1992 Sep, 19(9), 537 - 43
Enhancing effects of fluorescein on beta-lactam rash . II: Enhancing effects of fluorescein on generalized rash induced by beta-lactam antibiotics in guinea pigs; Ikezawa Z et al.; Healthy volunteers, who were receiving intravenous injections of cefclidin (CFCL) with frequent concomitant use of fluorescein (F) and oxybuprocain (O) in the eyes for measurement of ocular tension, developed drug eruptions at the high frequency of 66.7% . The injection of CFCL alone induced the eruptions at an incidence of 2.8% . The cause of this high eruption rate was thought to be the simultaneous treatment with F and/or O . Therefore, we conducted experiments with CFCL-induced generalized rash (GR) in guinea pigs . Guinea pigs treated with F and O during both the phases of immunization and intraperitoneal elicitation developed CFCL rashes at a high frequency . This CFCL-rash was augmented by the treatment with F during either phase, but not by the treatment with O . Skin testing induced delayed type hypersensitivity (DTH) reaction to O in some animals, but the DTH to F was not induced in animals immunized with F in complete Freund's adjuvant . Furthermore, F augmented rashes induced not only by CFCL but also by other beta-lactam antibiotics such as cefsulodin and sulbenicillin . Accordingly, it is likely that F played a dominant role in the high incidence of drug eruptions during the volunteer trials with measurement of ocular tension.

Eur J Clin Microbiol Infect Dis, 1992 Sep, 11(9), 823 - 7
Technique for calculation of the true costs of antibiotic therapy; Kerr JR et al.; An in-house method for costing antibiotic therapy is presented which quantifies hidden costs including costs arising from intravenous administration, labour, serum antibiotic assay, monitoring of haematological and biochemical indices and disposal of sharp instruments . A study of various hospital procedures relating directly to antibiotic therapy was undertaken in an acute medical ward, which involved determination of staff members performing various procedures, consumables used and time taken . Results of this study facilitated accurate quantification of hidden costs of i.v . antibiotic therapy in this ward . Using these results, the cost of five-day courses of gentamicin, cefuroxime, penicillin G, flucloxacillin and erythromycin were calculated . The costing of adverse effects was not attempted . It is recommended that a costing technique of this sort is used in cost-benefit analysis of antibiotic use, as the cost of the drug alone is misleading.

Analyst, 1992 Sep, 117(9), 1523 - 6
Flow injection spectrophotometric determination of the antibiotic ciprofloxacin in drug formulations; Sultan SM et al.; A flow injection spectrophotometric method for the assay of ciprofloxacin was developed . The method was based on the chelation of iron(III) with the drug in 0.023 mol dm-3 sulfuric acid solution in a 72 cm long coil and the brown-red complex produced was monitored at 447 nm . The super modified simplex computer program was employed for the optimization of the system and chemical parameters with respect to throughput and sensitivity as a measure of system performance . A working range for ciprofloxacin determination of 50-500 ppm for a 110 mm3 sample size with an optimum of 250 samples per hour was achieved with a relative standard deviation of less than 0.92% . The method was successfully applied to the determination of ciprofloxacin in drug formulations.

J Antibiot (Tokyo), 1992 Sep, 45(9), 1499 - 511
Biosynthesis of thiopeptide antibiotic A10255: incorporation of isotopically-labeled precursors; Favret ME et al.; The biosynthetic origin of antibiotic A10255 was investigated using 14C- and 13C-labeled amino acids . DL-{1-(13)C}Serine labeled 15 of the 17 amino acid residues present in A10255G . These included the oxazole, thiazole, dehydroalanine, masked glycine, masked alanine and pyridine moieties . The same 15 residues labeled by serine were labeled by {2-(13)C}glycine, apparently by conversion of the glycine to {2,3-(13)C}serine . Formation of the pyridine ring occurred via a C3 to C3 condensation of two serines . The results indicated origin of the masked alanine from alanine; the masked glycine from glycine; the thiazole residues from cysteine; and the threonine, masked dehydrobutyrine, masked dehydronorvaline and masked dehydroleucine residues from threonine . L(-){CH3-(13)C}Methionine labeled the methyl carbon of the masked dehydronorvaline moiety in factor B and the two methyl carbons of the masked dehydroleucine moiety in factor E . The results demonstrate that A10255 originates exclusively from amino acids in a manner similar to the closely related thiopeptide antibiotics nosiheptide and thiostrepton.

J Antibiot (Tokyo), 1992 Sep, 45(9), 1472 - 80
New antiviral antibiotics, cycloviracins B1 and B2 . II . Structure determination; Tsunakawa M et al.; The structures of novel antiviral antibiotics, cycloviracins B1 and B2 have been determined by means of chemical and spectroscopic methods including 2D NMR correlation spectroscopy . The antibiotics are unique macrocyclic diesters consisting of two D-glucoses, three 2-O-methyl-D-glucoses and two (C24 and C26) hydroxy fatty acids.

J Antibiot (Tokyo), 1992 Sep, 45(9), 1442 - 50
Butyrolactols A and B, new antifungal antibiotics . Taxonomy, isolation, physico-chemical properties, structure and biological activity; Kotake C et al.; New antifungal antibiotics, butyrolactols A and B, have been isolated from the culture broth of Streptomyces rochei S785-16 . They are novel type of molecules containing a common 2,3-dihydroxybutyrolactone nucleus substituted with a different long hydroxyalkyl side chain . Butyrolactol A showed good antifungal activity against Aspergillus fumigatus and Trichophyton mentagrophytes, and moderately inhibited the growth of yeasts.

J Antibiot (Tokyo), 1992 Sep, 45(9), 1433 - 41
Lactimidomycin, a new glutarimide group antibiotic . Production, isolation, structure and biological activity; Sugawara K et al.; Streptomyces amphibiosporus R310-104 (ATCC 53964) produced a novel antibiotic lactimidomycin which showed inhibitory activity against fungi and prolonged the survival time of mice transplanted with experimental tumors . Structural studies clarified that lactimidomycin is a new glutarimide antibiotic having a unique unsaturated 12-membered lactone ring.

Chem Phys Lipids, 1992 Sep, 62(2), 153 - 63
Interactions of aminoglycoside antibiotics with phospholipids . A deuterium nuclear magnetic resonance study; Schanck A et al.; The effect of several aminoglycoside (AG) antibiotics on aqueous multilamellar dispersions of mixtures of phosphatidylinositol (PI) and deuterated phosphatidylcholine (PC) has been studied by deuterium (2H) NMR . Isepamicin and amikacin gave rise to no significant changes in 2H-NMR lineshape relative to that of the lipid mixture without antibiotic . Both kanamycin A and B, which have a greater affinity for PI than the other two antibiotics examined in this study, induced temperature-dependent changes in 2H-NMR lineshapes and associated spectral moments . The results are consistent with an antibiotic-induced lateral phase separation giving rise to PC-enriched domains free of drug and PI-AG domains . These effects are correlated with the inhibitory potency of aminoglycosides towards PC degradation.

Chirurg, 1992 Sep, 63(9), 748 - 53
{Treatment of pilonidal sinus with excision and primary suture using a local, resorbable antibiotic carrier . Results of a prospective randomized study}; Vogel P et al.; The excision of a pilonidal sinus with wound healing by second intention, often results in a long duration of treatment . On the other hand, primary suture after excision has a high rate of abscess formation . In a randomized study we treated 40 patients with excision of pilonidal sinus, insertion of a collagen sponge containing Gentamicin and primary suture (group 1) to prevent this abscess formation . Another 40 patients were treated in the same way but without applying the Gentamicin-collagen sponge (group 2) . There had been no significant differences as to the history and duration of the disease, the wound size, the degree of inflammation, the weight of the patients or the amount of hair near the sinus . In group 1 only 7.5% of the patients had a postoperative abscess formation, in contrast to group 2, with an abscess rate of 52.5% and consecutive surgery (p less than 0.001) . One year after the operation the recurrence rate was 0 in both groups . Considering the results mentioned, surgical excision of the pilonidal sinus in combination with insertion of a resorbable antibiotic sponge we recommend this therapy.

Clin Orthop, 1992 Sep, (282), 241 - 9
Antibiotic-impregnated plaster of Paris beads . Trials with teicoplanin; Dacquet V et al.; Teicoplanin-impregnated plaster of Paris beads were made and in vitro release properties were studied . Teicoplanin was released in an initial massive dose, with a rapid decline during the first three days, followed by a slowly declining prolonged release up to 30 days . The release tested by diffusion in gelose and high-performance liquid chromatography was found to be 21.4% and 28.2%, respectively, of the amount theoretically present in the beads . Plaster of Paris is a resorbable, nontoxic biomaterial that has already been used to fill dead spaces in bone and deliver antibiotics in the treatment of chronic osteomyelitis . The addition of teicoplanin, a new antistaphylococcal agent with low known bacterial resistance, is a promising alternative . Follow-up tests in vivo, simulating local conditions of the osteomyelitic bone, are necessary to prove efficacy.

Trends Biotechnol, 1992 Sep, 10(9), 324 - 9
Genetic engineering of beta-lactam antibiotic biosynthetic pathways in filamentous fungi; Skatrud PL; Recombinant DNA technology has facilitated a rapid increase in our knowledge of beta-lactam antibiotic biosynthesis . Using the tools of this technology, beta-lactam biosynthetic genes and proteins have been characterized at the molecular level, cephalosporin-C production has been improved, new beta-lactams produced, and novel beta-lactam biosynthetic pathways have been constructed.

Am Fam Physician, 1992 Sep, 46(3), 863 - 9
New macrolide antibiotics: clarithromycin and azithromycin; Stott GA; Clarithromycin and azithromycin are new semisynthetic macrolide antibiotics structurally related to erythromycin . They are well absorbed and widely distributed, with excellent cellular and tissue penetration . Both have a broader spectrum of activity and fewer gastrointestinal side effects than erythromycin . Currently, clarithromycin and azithromycin are approved by the U.S . Food and Drug Administration for respiratory tract infections and skin infections, but they may also have use in mycobacterial and Toxoplasma infections in patients with acquired immunodeficiency syndrome.

Nippon Geka Hokan, 1992 Sep 1, 61(5), 387 - 95
Topical antibiotics in cholecystectomy for gallstone diseases; Aoki Y et al.; Efficacy of topical antibiotics in cholecystectomy for gallstone disease was evaluated . Forty-four patients who accepted topical single administration of 1 or 2 g each of latamoxef, cefmenoxime, cefotiam or cefamandole during operation were compared with 36 patients with systemic administration of cefem antibiotics by intravenous drip at a dose of 1 or 2 g, twice daily for postoperative 4 to 7 consecutive days . In topical administration group, concentration of each antibiotic in the gallbladder and common duct bile, gallbladder tissue, parietal peritonea and intra- and postoperative peripheral blood exceeded mostly MIC80 against bacteria usually existing in bile by biliary tract infection or bacteria by wound infection . There was no difference between the two groups in postoperative clinical course . Thus, an adequate prophylactic effect can be expected by topical use of antibiotic during cholecystectomy.

Allergol Immunopathol (Madr), 1992 Sep-Oct, 20(5), 184 - 9
Assessment of a self-designed protocol on patients with adverse reactions to beta-lactam antibiotics; Gonzalez J et al.; Suspected adverse reactions to beta-lactam antibiotics are the most frequent reason for consultation in relation WMH drug allergy . Because of their therapeutical usefulness and wide use, we developed a protocol for confirmation or exclusion of this type of allergy . The proposed protocol is based on clinical, causal and laboratory criteria that are used to assign scores from 0 to 9 points . Patients with scores between 0 and 3 are considered to be highly prone to beta-lactam antibiotic allergy and are given an alternative therapy that is selected by applying skin provocation tests (SPT) . Those with a score of 9 points are excluded . Finally, those with scores between 4 and 8 are subjected to skin tests with 5 antigens (penicillin G, ampicillin, cephalothin, Penkit PPL and Penkit MDM); if they give negative results they are subsequently subjected to oral provocation with beta-lactam antibiotics . In this work we report the results obtained from 150 patients analysed for 28 variables altogether . The results allowed us to rule out adverse reactions in 94 patients . Only 9 individuals yielded positive skin tests, and only one gave a positive oral provocation (bronchospasm, 6 hours after subjection to the test) . The usefulness of the proposed protocol, the profitability of the test applied and the mechanisms involved are assessed.

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