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| Biochemistry, 2004 Dec 28, 43(51), 16497 - 504 Binding of antitumor antibiotic daunomycin to histones in chromatin and in solution; Rabbani A et al.; Daunomycin is an anticancer drug that is well-known to interact with DNA in chromatin . Using a compositionally defined chicken erythrocyte chromatin fraction, we have obtained conclusive evidence that the drug is also able to interact with chromatin-bound linker histones without any noticeable binding to core histones . The drug can interact in an equal fashion with both histone H1 and H5 and to a greater extent with core histones H3/H4 and H2A/H2B as free proteins in solution . Thus, the binding of daunomycin to linker histones in the chromatin fiber is most likely due to the well-known higher accessibility of these histones to the surrounding environment of the fiber . Binding of daunomycin to linker histones appears to primarily involve the trypsin-resistant (winged-helix) domain of these proteins . The studies described here reveal the occurrence of a previously undisclosed mechanism for the antitumor activity of anthracycline drugs at the chromatin level. J Chromatogr B Analyt Technol Biomed Life Sci, 2005 Jan 5, 814(1), 75 - 81 Analysis of benidipine enantiomers in human plasma by liquid chromatography-mass spectrometry using a macrocyclic antibiotic (Vancomycin) chiral stationary phase column; Kang W et al.; We used a novel chromatographic method to rapidly and simply characterize the pharmacokinetics of benidipine enantiomers in human plasma . The stereoisomers of benidipine were extracted from plasma using diethylether under alkaline conditions . After evaporating the organic layer, the residue was reconstituted in the mobile phase (methanol:acetic acid:triethylamine, 100:0.01:0.0001, v/v/v) . The enantiomers in the extract were separated on a macrocyclic antibiotic (Vancomycin) chiral stationary phase column . The mobile phase was eluted at 1ml/min and was split by an interface . One-fifth of the eluent was used to quantify both isomers in a tandem mass spectrometer in multiple reaction-monitoring mode . The coefficient of variation of the precision of the assay was less than 8%, the assay accuracy was between 93.4 and 113.3%, and the limit of detection was 0.05ng/ml for 1ml of plasma . The method described above was used to measure the concentration of both benidipine enantiomers in plasma from healthy subjects who received a single oral dose of a racemate of 8mg benidipine . The C(max) and AUC(inf) values of (+)-alpha benidipine were higher than those of (-)-alpha benidipine by 1.96- and 1.85-fold, respectively (p<0.001), whereas, the T(max) and t(1/2) for each of the benidipine stereoisomers were not significantly different. Med Hypotheses, 2005, 64(2), 312 - 5 Could one of the most widely prescribed antibiotics amoxicillin/clavulanate "augmentintrade mark" be a risk factor for autism? Fallon J. Autism is an ever increasing problem in the United States . Characterized by multiple deficits in the areas of communication, development, and behavior; autistic children are found in every community in this country and abroad . Recent findings point to a significant increase in autism which can not be accounted for by means such as misclassification . The state of California recently reported a 273% increase in the number of cases between 1987 and 1998 . Many possible causes have been proposed which range from genetics to environment, with a combination of the two most likely . Since the introduction of clavulanate/amoxicillin in the 1980s there has been the increase in numbers of cases of autism . In this study 206 children under the age of three years with autism were screened by means of a detailed case history . A significant commonality was discerned and that being the level of chronic otitis media . These children were found to have a mean number 9.96 bouts of otitis media (with a standard error of the mean of +/-1.83) . This represents a sum total for all 206 children of 2052 bouts of otitis media . These children received a mean number of 12.04 courses of antibiotics (standard error of the mean of +/-.125) . The sum total number of courses of antibiotics given to all 206 children was 2480 . Of those 893 courses were Augmentin . with 362 of these Augmentin courses administered under the age of one year . A proposed mechanism whereby the production of clavulanate may yield high levels of urea/ammonia in the child is presented . Further an examination of this mechanism needs to be undertaken to determine if a subset of children are at risk for neurotoxicity from the use of clavulanic acid in pharmaceutical preparations. J Obstet Gynaecol Can, 2004 Dec, 26(12), 1067 - 72 Prophylactic antibiotics for abdominal hysterectomy: indication for low-risk canadian women; Eason EL et al.; OBJECTIVE: To determine whether prophylactic antibiotics decrease the risk of infectious morbidity after total abdominal hysterectomy (TAH) in women at low risk for infection . Methods: An analysis of data from 1570 women undergoing planned TAH at 15 secondary and tertiary hospitals in Nova Scotia, Ontario, and Quebec, who agreed to participate in a centrally randomized controlled trial of vaginal antisepsis with povidone-iodine gel compared to no gel after the standard preoperative vaginal preparation with povidone-iodine solution . RESULTS: Prophylactic antibiotics were used in 993 of 1570 women (63%) . Appropriately timed prophylactic antibiotics decreased infectious morbidity (odds ratio {OR}, 0.65; 95% confidence interval {CI}, 0.50-0.85; P < .002).After controlling for risk factors for infection and study centre, the protective effect was even more pronounced (adjusted OR, 0.51; 95% CI, 0.36-0.73) . Prophylactic antibiotics were associated with decreases in abdominal wound infection (OR, 0.45; 95% CI, 0.30-0.66) and pelvic infection (OR, 0.49; 95% CI, 0.26-0.92) . CONCLUSION: Women who did not receive prophylactic antibiotics had a higher surgical infection rate . Prophylactic antibiotics should be recommended for all women undergoing TAH. East Mediterr Health J, 2002 Jul-Sep, 8(4-5), 638 - 44 Management of wound infection after appendectomy: are parenteral antibiotics useful? Harahsheh B, Hiyasat B, Abulail A, Al-Basheer M. This study investigated the use of antibiotics in the treatment of wound infections after appendectomy . The subjects were 72 patients with post-operative wound infections at a district general hospital in Jordan . All patients received daily antiseptic dressings with povidone-iodine 10% in alcohol . The patients were randomized in a single-blind trial to receive either no antibiotics or parenteral antibiotics metronidazole and cefoxitin . There was no significant effect of antibiotic use in patients with early inflamed or severely inflamed appendicitis . However, for patients with perforated appendicitis the mean length of hospital stay and the mean frequency of change of dressings were significantly reduced . We conclude that antibiotics do not offer any advantage in post-appendectomy wound infections except for cases of perforated appendix. Arch Anim Nutr, 2004 Oct, 58(5), 367 - 78 Performance and caecal adaptation of turkeys to diets without or with antibiotic and with different levels of mannan-oligosaccharide; Zdunczyk Z et al.; A study on turkeys was conducted to evaluate the administration of different levels of mannan-oligosaccharide (MOS) (0.1, 0.25 and 0.5%) to a diet without or with an antibiotic (Flavomycin, 8 mg/kg feed) . The growth performance as well as caecal development and metabolism indicators of turkeys after 8 weeks of experimental feeding were estimated . No interactions were noted between the contents of antibiotic and MOS in the diet in any of the parameters examined . During 8 weeks of experimental feeding, the feed intake as well as feed conversion ratio were similar in all experimental groups . The turkeys fed a control diet (without MOS) supplemented with antibiotic were the heaviest, but there were no statistical differences between groups . Depending on dietary dose, MOS had a different influence on caecal digesta parameters . The medium level of dietary MOS (0.25%) resulted in the highest caecal pH, dry matter and protein concentrations as well as the bacterial glycolytic activity (including beta-glucuronidase) . Compared to other dietary treatments, the highest amount of MOS (0.5%) reduced ammonia concentration and enhanced volatile fatty acids concentration, especially of acetate and butyrate, in the caecal digesta . The medium level of dietary MOS caused a significant enhancement of propionate, iso-butyrate and iso-valerate concentrations in the digesta . The antibiotic addition to a diet resulted in a lack of birds' response. Rapid Commun Mass Spectrom . 2004 Dec 13;19(2):209-212 {Epub ahead of print} Probing the interaction of kojic acid antibiotics with iron(III) chloride by using electrospray tandem mass spectrometry; Sudhir PR et al.; Kojic acid, 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one, has been used extensively as a clinical iron-chelating drug although the nature of the complexes of iron and kojic acid has not been established . In this article we demonstrate the complexation of kojic acid with iron(III) chloride by using electrospray ionization mass spectrometry (ESI-MS) . The ESI-MS analysis revealed different reactions between iron(III) chloride and kojic acid (M), and the mass spectrum exhibited four complexes: {Fe+2(M--H)}(+), {Fe+3(M--H)+H}(+), {Fe(2)+4(M--H)+Cl}(+), and {Fe(2)+5(M--H)}(+) . All these proposed complexes and the presence of chloride ion in one of the dinuclear complexes have been confirmed by isotopic patterns and fragmentation studies by means of tandem mass spectrometry (MS(n)) . Copyright (c) 2004 John Wiley & Sons, Ltd. Injury, 2005 Jan, 36(1), 199 - 202 Local antibiotics: panacea for long term skeletal traction; Nigam V et al.; Long periods of skeletal traction are frequently needed in busy tertiary centres due to long waiting lists for surgery . A frequent complication is pin track infection, which leads to revision of pin insertion or switching over to skin traction . A prospective study was conducted on sixty patients with upper tibial pin insertion for various causes . Antibiotic (injection Cephazolin 0.5g after sensitivity testing-250mg on each side) was injected on thirty patients at the site of pin insertion and no antibiotic was injected in 30 controls . Only one stage one pin track infection was seen in the study group (3% cases), where as six cases had stage 1 infection, one case had stage 2 infection and two cases had stage 3 infections in the control group (30% cases) . This study showed the usefulness of this modification in preventing morbidity in patients who are planned for long-term skeletal traction by temporarily suppressing the local flora. Soc Sci Med, 2005 Mar, 60(5), 949 - 64 Non-antibiotic treatment recommendations: delivery formats and implications for parent resistance; Stivers T; This study draws on a database of 570 community-based acute pediatric encounters in the USA and uses conversation analysis as a methodology to identify two formats physicians use to recommend non-antibiotic treatment in acute pediatric care (using a subset of 309 cases): recommendations for particular treatment (e.g., "I'm gonna give her some cough medicine.") and recommendations against particular treatment (e.g., "She doesn't need any antibiotics.") . The findings are that the presentation of a specific affirmative recommendation for treatment is less likely to engender parent resistance to a non-antibiotic treatment recommendation than a recommendation against particular treatment even if the physician later offers a recommendation for particular treatment . It is suggested that physicians who provide a specific positive treatment recommendation followed by a negative recommendation are most likely to attain parent alignment and acceptance when recommending a non-antibiotic treatment for a viral upper respiratory illness. Environ Pollut, 2005 Mar, 134(2), 333 - 41 A lysimeter experiment to investigate the leaching of veterinary antibiotics through a clay soil and comparison with field data; Kay P et al.; Pharmaceuticals used in livestock production may be present in manure and slurry as the parent compound and/or metabolites . The environment may therefore be exposed to these substances due to the application of organic fertilisers to agricultural land or deposition by grazing livestock . For other groups of substances that are applied to land (e.g . pesticides), preferential flow in clay soils has been identified as an extremely important mechanism by which surface water pollution can occur . This lysimeter study was therefore performed to investigate the fate of three antibiotics from the sulphonamide, tetracycline and macrolide groups in a clay soil . Only sulphachloropyridazine was detected in leachate and soil analysis at the end of the experiment showed that almost no antibiotic residues remained . These data were analysed alongside field data for the same compounds to show that soil tillage which breaks the connectivity of macropores formed over the summer months, prior to slurry application, significantly reduces chemical mobility. Physiol Res, 2004, 53(6), 683 - 91 The effect of new lipophilic chelators on the activities of cytosolic reductases and P450 cytochromes involved in the metabolism of anthracycline antibiotics: studies in vitro; Schroterova L et al.; A major obstacle to the therapeutic use of anthracyclines, highly effective anticancer agents, is the fact that their administration results in dose-dependent cardiomyopathy . According to the currently accepted hypothesis, anthracyclines injure the heart by generating oxygen free radicals . The ability of pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde isonicotinoyl hydrazone (SIH) - new iron chelators - to protect against peroxidation as well as their suitable biological, physical and chemical properties make the compounds promising candidates for pre-clinical and clinical studies . Activities of carbonyl reductase CR (1.1.1.184), dihydrodiol dehydrogenase DD2 (1.3.1.20), aldehyde reductase ALR1 (1.1.1.2) and P450 isoenzymes (CYP1A1, CYP1A2, CYP2B, CYP3A) involved in the metabolism of daunorubicin, doxorubicin and other drugs or xenobiotics were studied . Various concentrations of the chelators were used either alone or together with daunorubicin or doxorubicin for in vitro studies in isolated hepatocytes . A significant decrease of activity was observed for all enzymes only at PIH and SIH concentrations higher than those presumed to be used for therapy . The results show that PIH and SIH have no effect on the activities of the enzymes studied in vitro and allow us to believe that they will not interfere with the metabolism of co-administered drugs and other xenobiotics . Daunorubicin (Da) and doxorubicin (Dx) significantly reduce cytochrome P450 activity, but the addition of SIH and PIH chelators (50 microM) reverses the reduction and restores the activity to 70-90 % of the activity of relevant controls. J Infus Nurs, 2004 Nov-Dec, 27(6), 425 - 30 Home intravenous antibiotic therapy and allergic drug reactions: is there a case for routine supply of anaphylaxis kits? Dobson PM, Boyle M, Loewenthal M. This study aimed to estimate the risk of an allergic reaction for patients receiving home intravenous antibiotics, and to identify the potential advantages and disadvantages of providing injectable epinephrine in this patient population . In this study, 770 patients received 1000 courses of home intravenous therapy with 25 different antibiotics for 37 conditions . The patients in the program experienced 28 allergic reactions . The mean time to allergic reaction was 19.6 days . No episodes of anaphylaxis were observed . These results, coupled with the potential disadvantages of issuing epinephrine to all patients receiving home antibiotic therapy, suggest that this strategy may not provide a net benefit. Pharmacotherapy, 2004 Dec, 24(12 Pt 2), 224S - 31S The impact of antibiotic management on resistance; Bosso JA; The misguided presumption that a simple inverse relationship exists between the use of antibiotics and the emergence of bacterial resistance (i.e., increasing antibiotic use equals decreasing susceptibility and vice versa) has handicapped a full understanding of this relationship and perhaps efforts to bring resistance under control . In fact, this relationship is complicated . This article reviews factors that obscure detection of associations between antibiotic use and the emergence of resistance . It also provides a sample of the extensive data on this subject in the hope of encouraging the conduct of more sophisticated studies of the relationship between antibiotic use and the emergence of resistance . Such studies are necessary to provide institutions with the data they need to make informed decisions regarding antibiotic use. Biomaterials, 2005 May, 26(15), 2677 - 84 Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections; Rauschmann MA et al.; The use of polymethylmetacrylate beads for local delivery of antibiotics requires a second surgical procedure for their removal and resorbable calcium sulphate exhibits cytotoxic effects . In this work, a bioresorbable composite of calcium sulphate and nanoparticulate hydroxyapatite (PerOssal((R))) was studied regarding its antibiotic release properties and biocompatibility . Material characteristics of plain PerOssal((R)) and pure calcium sulphate pellets were studied using scanning and electron microscopy and X-ray methods . Pellets were soaked with gentamicin and vancomycin, respectively . Release properties of both antibiotics from both materials were investigated over 10 days . Quantitative and qualitative cytotoxic assays were performed for biocompatibility testing . Specific surface was 106m(2)/g for PerOssal((R)) and 2.2m(2)/g for pure calcium sulphate . Almost complete elution of gentamicin was found for both carrier materials (94.7% for PerOssal((R)) vs . 95.8% for calcium sulphate) within 10 days, whereas vancomycin release was higher for PerOssal((R)) (96.3% vs . 74.8%) . PerOssal((R)) showed higher initial and lower release after approximately 5 days compared to calcium sulphate . No significant in vitro cytotoxic differences were found between PerOssal((R)) and nontoxic cell culture medium . Calcium sulphate showed cytotoxic effects in two out of four tests . PerOssal((R)) exhibits excellent properties regarding resorption, biocompatibility, and antibiotic release. Eur J Intern Med, 2004 Nov, 15(7), 441 - 445 Adverse drug reactions due to prolonged antibiotic therapy for malignant external otitis; Shichmanter R et al.; BACKGROUND: Malignant external otitis (MEO) is a life-threatening infection requiring prolonged antibiotic therapy . Adverse drug reactions (ADR) occur frequently in patients treated with long-term antibiotics, often limiting treatment effectiveness . We attempted to identify and categorize the frequency and type of ADR in patients undergoing treatment for MEO in an attempt to improve overall treatment of individuals with this disorder . METHODS: Twenty-one patients with MEO who were treated during a 10-year period at our institution were identified retrospectively . Records were reviewed to determine demographic and clinical information as well as laboratory data . RESULTS: Overall, ADR occurred in six individuals (26.8%) . Of the 15 patients who received ciprofloxacin therapy, none experienced ADR . In contrast, six of the nine patients who were treated with beta-lactam antibiotics experienced ADR including urticaria, elevated serum transaminase levels and neutropenia . CONCLUSIONS: Prolonged antibiotic therapy for MEO with beta-lactam antibiotics is more likely to be complicated by ADR and requires careful monitoring. Biochemistry, 2004 Dec 14, 43(49), 15550 - 6 Effects of the antibiotic pulvomycin on the elongation factor Tu-dependent reactions . Comparison with other antibiotics; Anborgh PH et al.; The antibiotic pulvomycin is an inhibitor of protein synthesis that prevents the formation of the ternary complex between elongation factor (EF-) Tu.GTP and aminoacyl-tRNA . In this report, novel aspects of its action on EF-Tu are described . Pulvomycin markedly affects the equilibrium and kinetics of the EF-Tu-nucleotide interaction, particularly of the EF-Tu.GTP complex . The binding affinity of EF-Tu for GTP is increased 1000 times, mainly as the consequence of a dramatic decrease in the dissociation rate of this complex . In contrast, the affinity for GDP is decreased 10-fold due to a marked increase in the dissociation rate of EF-Tu.GDP (25-fold) that mimics the action of EF-Ts, the GDP/GTP exchange factor of EF-Tu . The effects of pulvomycin and EF-Ts can coexist and are simply additive, supporting the conclusion that these two ligands interact with different sites of EF-Tu . This is further confirmed on native PAGE by the ability of EF-Tu to bind the EF-Ts and the antibiotic simultaneously . Pulvomycin enhances the intrinsic EF-Tu GTPase activity, like kirromycin, though to a much more modest extent . As with kirromycin, this stimulation depends on the concentration and nature of the monovalent cations, Li(+) being the most effective one, followed by Na(+), K(+), and NH(4)(+) . In the presence of pulvomycin (in contrast to kirromycin), aa-tRNA and/or ribosomes do not enhance the GTPase activity of EF-Tu . The property of pulvomycin to modify selectively the conformation(s) of EF-Tu is also supported by its effect on heat- and urea-dependent denaturation, and tryptic digestion of the protein . Specific differences and similarities between the action of pulvomycin and the other EF-Tu-specific antibiotics are described and discussed. J Antibiot (Tokyo), 2004 Sep, 57(9), 590 - 6 Suppressive effect of antibiotic siomycin on antibody production; Ueno M et al.; The antibiotic thiazole compound siomycin, which we have found from the culture broth of Actinomycetes (strain No.806097) in search of antibody production inhibitor, showed the in vitro immunosuppressive property against B-cells stimulated with T-cell independent antigen DNP-LPS (dinitrophenyl-lipopolysaccharide) while it also showed inhibitory effect against T-cell proliferation . Its inhibitory mechanism was considered to be different from that of FK506, the representative of T-cell immunosuppressant . Moreover, siomycin showed inhibitory effect in both T-cell dependent and independent murine antibody production models and decreased the severity in murine collagen arthritis model . Therefore, siomycin is a unique immunosuppressant which has potential for the treatment of some antibody-mediated diseases. Genetics, 2004 Nov, 168(3), 1131 - 44 Combining mathematical models and statistical methods to understand and predict the dynamics of antibiotic-sensitive mutants in a population of resistant bacteria during experimental evolution; De Gelder L et al.; Temporarily discontinuing the use of antibiotics has been proposed as a means to eliminate resistant bacteria by allowing sensitive clones to sweep through the population . In this study, we monitored a tetracycline-sensitive subpopulation that emerged during experimental evolution of E . coli K12 MG1655 carrying the multiresistance plasmid pB10 in the absence of antibiotics . The fraction of tetracycline-sensitive mutants increased slowly over 500 generations from 0.1 to 7%, and loss of resistance could be attributed to a recombination event that caused deletion of the tet operon . To help understand the population dynamics of these mutants, three mathematical models were developed that took into consideration recurrent mutations, increased host fitness (selection), or a combination of both mechanisms (full model) . The data were best explained by the full model, which estimated a high mutation frequency (lambda = 3.11 x 10(-5)) and a significant but small selection coefficient (sigma = 0.007) . This study emphasized the combined use of experimental data, mathematical models, and statistical methods to better understand and predict the dynamics of evolving bacterial populations, more specifically the possible consequences of discontinuing the use of antibiotics. J Org Chem, 2004 Dec 10, 69(25), 8594 - 601 Complex peptidyl nucleoside antibiotics: efficient syntheses of the glycosyl nucleoside amino acid cores; Bhaket P et al.; Employing an amino acid chiral template strategy, the present research describes a general and highly efficient protocol for the rapid construction of enantiopure furanosyl and pyranosyl nucleoside amino acid cores as present in various complex peptidyl nucleoside antibiotics . Starting from easily available d-serine, the strategy and the approach involve rapid and efficient stereoselective synthesis of five- or six-membered lactone amino alcohols, followed by incorporation of the required functionalities of the target molecules on these strategically functionalized chiral templates. J Antimicrob Chemother, 2005 Jan, 55(1), 1 - 5 Epub 2004 Dec 01. Antibiotic cycling: more than it might seem? Masterton RG. In the present battle against the rising tide of resistance, several interventions have been proposed to help control the situation . One of these is a process of planned antibiotic restriction, introduced through cycling drug selection based on local surveillance . Although such antibiotic cycling has been the subject of much discussion for 20 years, there are relatively few data available to assess its worth . A recent systematic review found only four studies worthy of inclusion and concluded that antibiotic cycling could not, at present, be promoted as a methodology to control resistance . This paper considers the complete literature and through demonstrating consistent benefits across the breadth and depth of the findings, suggests that whereas further work is required, nevertheless antibiotic cycling-as part of a suite of control measures-is a valid option. BMC Fam Pract . 2004 Dec 01;5(1):28. Caregivers' practices, knowledge and beliefs of antibiotics in paediatric upper respiratorytract infections in Trinidad and Tobago: a cross-sectional study; Parimi N et al.; BACKGROUND: Antibiotic overuse and misuse for upper respiratory tract infections in children is widespread and fuelled by public attitudes and expectations . This study assessed knowledge, beliefs, and practices regarding antibiotic use for these paediatric infections among children's caregivers' in Trinidad and Tobago in the English speaking Caribbean . METHODS: In a cross-sectional observational study, by random survey children's adult caregivers gave a telephone interview from November 1998 to January 1999 . On a pilot-tested evaluation instrument, respondents provided information about their knowledge and beliefs of antibiotics, and their use of these agents to treat recent episodes (< previous 30 days) of upper respiratory tract infections in children under their care . Caregivers were scored on an antibiotic knowledge test and divided based on their score . Differences between those with high and low scores were compared using the chi-square test . RESULTS: Of the 417 caregivers, 70% were female and between 18-40 years, 77% were educated to high school and beyond and 43% lived in urban areas . Two hundred and forty nine (60%) respondents scored high (>or12) on antibiotic knowledge and 149 (34%) had used antibiotics in the preceding year . More caregivers with a high knowledge score had private health insurance (33%), (p < 0.02), high school education (57%) (p < 0.002), and had used antibiotics in the preceding year (p < 0.008) and within the last 30 days (p < 0.05) . Caregivers with high scores were less likely to demand antibiotics (p < 0.05) or keep them at home (p < 0.001), but more likely to self-treat with antibiotics (p < 0.001) . Caregivers administered antibiotics in 241/288 (84%) self-assessed severe episodes of infection (p < 0.001) and in 59/126 (43%) cough and cold episodes without visiting a health clinic or private physician (p < 0.05) . CONCLUSIONS: In Trinidad and Tobago, caregivers scoring low on antibiotic knowledge have erroneous beliefs and use antibiotics inappropriately . Children in their care receive antibiotics for upper respiratory tract infections without visiting a health clinic or a physician . Educational interventions in the community on the consequences of inappropriate antibiotic use in children are recommended . Our findings emphasise the need to address information, training, legislation and education at all levels of the drug delivery system towards discouraging self-medication with antibiotics in children. Drug Chem Toxicol, 2004 Nov, 27(4), 295 - 307 Safety pharmacology of DW-224a, a novel fluoroquinolone antibiotic agent; Kim EJ et al.; To investigate the safety pharmacology of a novel fluoroquinolone antibiotic agent, DW-224a, on the vital functions, we studied its effects on the central nervous system, cardiovascular system and respiratory system . To determine the effects on the central nervous system, we used a modified Irwin's test at each time point after oral administration of DW-224a to mice . In this test, we found that the treatment of test article had no effects on motor activity, behavioral changes, coordination, and sensory/motor reflex responses . The effects of DW-224a on the cardiovascular system were evaluated by the use of a telemetry system in beagle dogs . At 360 min post-DW-224a (100 mg/kg) administration, QT interval prolongation was observed . However, there were no changes in heart rate, blood pressure, and electrocardiogram at all doses and each time points with the exception of QT-interval prolongation as compared to the vehicle treated group . In experiments designed to determine the changes of respiratory function in rats, we found no changes at all doses and time points . We investigated the effects of DW-224a on the human ether-a-go-go-related gene (hERG) mediated potassium currents to evaluate its potential to induce QT interval prolongation . When whole cell patch-clamp electrophysiology was used, DW-224a inhibited hERG currents with IC50 of 218.12 +/- 39.51 microM though its effect was less potent than that of E-4031, a positive control drug . Our data suggested that DW-224a showed no adverse effects on the central nervous system, cardiovascular system, and respiratory system, with the exception of the effect on the QT interval prolongation. Nucleosides Nucleotides Nucleic Acids, 2004 Oct, 23(8-9), 1305 - 11 Immucillins as antibiotics for T-cell proliferation and malaria; Schramm VL; The genetic deficiency of human PNP causes a specific immunodeficiency by inducing apoptosis in dividing T-cells . Powerful inhibitors of PNP have been designed from the experimental determination of the transition state structure of PNPs . The Immucillins are transition state analogue inhibitors with Kd values as low as 7 pM . In the presence of deoxyguanosine the Immucillins kill activated human T-cells but not other cell types . The Immucillins are orally available and of low toxicity to mice . Immucillins also inhibit PNP from Plasmodium falciparum . Parasites cultured in human erythrocytes are killed by purine starvation in the presence of Immucillins and can be rescued by hypoxanthine. J Biol Chem . 2004 Nov 29; {Epub ahead of print} Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes; Schmoock G et al.; Quinoxaline antibiotics are chromopeptide lactones embracing the two families of triostins and quinomycins, each having characteristic sulfur-containing cross-bridges . Interest in these compounds stems from their antineoplastic activities and their specific binding to DNA via bifunctional intercalation of the twin chromophores represented by quinoxaline-2-carboxylic acid (QA).1 Enzymatic analysis of triostin A-producing Streptomyces triostinicus and quinomycin A-producing Streptomyces echinatus revealed four nonribosomal peptide synthetase (NRPS) modules for the assembly of the quinoxalinoyl tetrapeptide backbone of the quinoxaline antibiotics . The modules were contained in three protein fractions, referred to as triostin synthetases (TrsII, III and IV) . TrsII is a 245 kDa bimodular NRPS activating as thioesters both serine and alanine, the first two amino acids of the quinoxalinoyl tetrapeptide chain . TrsIII, represented by a protein of 250 kDa, activates cysteine as a thioester . TrsIV, an unstable protein of apparent Mr ca . 280,000, was identified by its ability to activate and N-methylate valine, the last amino acid . QA, the chromophore, was shown to be recruited by a free-standing adenylation domain, TrsI, in conjunction with a QA-binding protein, AcpPSE . Cloning of the gene for the QA-binding protein revealed that it is the fatty acyl carrier protein, AcpPSE, of the fatty acid synthase of S . echinatus and S . triostinicus . Analysis of the acylation reaction of AcpPSE by TrsI along with other A-domains and the aryl carrier protein AcmACP from actinomycin biosynthesis revealed a specific requirement for AcpPSE in the activation and also in the condensation of QA with serine in the initiation step of QA tetrapeptide assembly on TrsII . These data show for the first time a functional interaction between nonribosomal peptide synthesis and fatty acid synthesis. Eur J Pharm Biopharm, 2005 Jan, 59(1), 17 - 24 Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1; Luckner P et al.; The activity of the renal peptide transporters PEPT2 and PEPT1 determines-among other factors such as metabolic stability in liver and plasma-the circulatory half-life of penicillins and cephalosporins during therapy . This study was initiated to examine systematically the interaction of beta-lactam antibiotics with PEPT2 . Interaction of 31 cephalosporins and penicillins with the carrier protein was characterized by measuring their ability to inhibit the uptake of {(14)C}Gly-Sar into renal SKPT cells . Cefadroxil, cefaclor, cyclacillin, cephradine, cephalexin and moxalactam were recognized by PEPT2 with very high affinity comparable to that of natural dipeptides (K(i)=3-100microM) . Ceftibuten, dicloxacillin, amoxicillin, metampicillin, cloxacillin, ampicillin, cefixime, cefamandole, oxacillin and cefmetazole interacted with PEPT2 with medium affinity (K(i)=0.1-5mM) . For the other beta-lactam antibiotics studied interaction was very low or not measurable (K(i)>5mM) . The affinity constants of beta-lactam antibiotics at rPEPT2 and hPEPT1 are significantly correlated, but the rank orders are not identical . Decisive differences between PEPT1 and PEPT2 recognition of the N-terminal part of the compounds became evident . Moreover, this large data set of affinity constants of beta-lactam antibiotics will be useful for structure-transport (binding) analyses of PEPT2. J Neural Transm, 2004 Dec, 111(12), 1523 - 35 Epub 2004 Dec. Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release; Ohtaki K et al.; Cefoselis is a widely used beta-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients . However, beta-lactams are known not to pass through the blood-brain barrier (BBB) . In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis . Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level . The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood . These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system . In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection . In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged . This would be one of responsible factors inducing seizures seen in patients . However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats . A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in gamma-aminobutyric acid (GABA) . However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures . These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis. Eur J Dermatol, 2004 Nov-Dec, 14(6), 391 - 9 European recommendations on the use of oral antibiotics for acne; Dreno B et al.; Non-rational prescribing of oral antibiotics in acne is common, and there is currently an unmet need for up-to-date guidelines that specifically address these issues . Presented here is a set of recommendations on the use of oral antibiotics in acne, developed by a group of European acne specialists, designed to be considered by dermatologists and general practitioners in their daily practice throughout Europe . Recommendations cover optimal choice of antibiotic, drug doses, duration of treatment, combination treatment, and maintenance therapy. Antimicrob Agents Chemother, 2004 Dec, 48(12), 4878 - 81 Glucocorticoids increase in vitro and in vivo activities of antibiotics against Chlamydophila pneumoniae; Caronzolo D et al.; The in vitro and in vivo antichlamydial activities of dexamethasone and beclomethasone alone and in combination with an antibiotic were tested . In vitro, dexamethasone and beclomethasone decreased the number of inclusion-forming units versus the control number (P < 0.001) . The combination of glucocorticoids with azithromycin, telithromycin, or levofloxacin was more active than antibiotics used alone (P < 0.001) . The combination, tested in a murine Chlamydophila pneumoniae infection model, produced similar results. Antimicrob Agents Chemother, 2004 Dec, 48(12), 4822 - 8 Evaluation of antibiotic susceptibilities of Ehrlichia canis, Ehrlichia chaffeensis, and Anaplasma phagocytophilum by real-time PCR; Branger S et al.; We determined MICs of antibiotics against Anaplasma phagocytophilum, Ehrlichia chaffeensis, and Ehrlichia canis by real-time quantitative PCR . The doubling times of the organisms were established: 19 h for E . chaffeensis, 26 h for A . phagocytophilum, and 28 h for E . canis . In comparison to the reference method for determining sensitivities, which uses Diff-Quick staining, our PCR assay was very sensitive and specific . We confirmed that doxycycline and rifampin are highly active against these bacteria and found variable susceptibilities to fluoroquinolones; A . phagocytophilum was susceptible, but E . canis and E . chaffeensis were only partly susceptible . Beta-lactam compounds, cotrimoxazole, macrolide compounds, and telithromycin showed no activity against any of the three organisms . Thiamphenicol was found to be more active than chloramphenicol . For the first time, we showed that these three species have numerous point mutations in their 23S RNA genes, with those at positions 754, 2057, 2058, 2059, and 2611 (Escherichia coli numbering) known to confer resistance to macrolide compounds in other bacteria . The role of each of these mutations in resistance to these drugs should be investigated in the future . Our study confirms previous reports that quantitative PCR is a reliable method for determining antibiotic susceptibility; therefore, it might be useful for screening new drugs. J Enzyme Inhib Med Chem, 2004 Aug, 19(4), 361 - 5 Effects of some antibiotics on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro and in vivo study; Akyuz M et al.; The in vitro and in vivo effects of some antibiotics on human erythrocyte 6-phosphogluconate dehydrogenase were investigated . Human erythrocyte 6-phosphogluconate dehydrogenase was purified with ammonium sulphate precipitation, 2',5' ADP-Sepharose 4B affinity and gel filtration chromatography . Some antibiotics (netilmicin sulphate, cefepime, amikacin, isepamycin, chloramphenicol, ceftazidim, teicoplanin, ampicillin, ofloxacin, levofloxacin, cefotaxime, penicillin G, gentamicin sulphate, ciprofloxacin) inhibited enzyme activity in vitro but others (cefozin, decefin, streptomycin, combisid, and meronem) were devoid of inhibitory effects . For the drugs having low IC50 values (netilmicin sulphate and cefepime), in vivo studies were performed in rats . Netilmicin sulphate at 15-mg/kg inhibited enzyme activity significantly (p < 0.001) 1 h, 2 h, and 3 h after dosing and cefepime at 200-mg/kg very significantly (p < 0.001) inhibited the enzyme 1 h and 2 h after dosing . Netilmicin sulphate and cefepime inhibited rat erythrocyte 6-phosphogluconate dehydrogenase both in vivo and in-vitro. Mar Pollut Bull, 2004 Dec, 49(11-12), 922 - 9 Residues of selected antibiotics in water and mud from shrimp ponds in mangrove areas in Viet Nam; Le TX et al.; In recent years, antibiotics have been used widely in intensive shrimp culture and this may lead to their contamination of the environment . Surveys on residues of trimethoprim (TMP), sulfamethoxazole (SMX), norfloxacin (NFXC) and oxolinic acid (OXLA) in water and mud in shrimp ponds in mangrove areas were conducted in the north as well as in south of Viet Nam in July and August, 2002 . The results show that these antibiotics are found in all samples in both shrimp ponds and surrounding canals . The highest concentrations of TMP, SMX, NFXC and OXLA are 1.04, 2.39, 6.06, and 2.50 ppm in water samples; and 734.61, 820.49, 2615.96, 426.31 ppm (based on wet mud weight), respectively . The comparison of antibiotics residues between study sites and types of shrimp ponds will be discussed in this paper . The results also suggest that antibiotics residues may cause harmful effect on ecosystems in the study sites. Int J Antimicrob Agents, 2004 Dec, 24(6), 550 - 4 Efficacy of long-term macrolide antibiotic therapy in patients with diffuse panbronchiolitis: comparison between HLA-B54-positive and -negative cases; Kadota J et al.; This study compared the clinical characteristics and the effects of long-term macrolide antibiotic therapy of HLA-B54-positive and -negative cases in patients with diffuse panbronchiolitis (DPB) . Thirty-two Japanese patients were enrolled who had the clinical criteria for DPB . All patients received long-term macrolide therapy, and therapeutic results were compared according to the presence or the absence of HLA-B54 antigen . Clinical, laboratory, radiological and bacterial features were strikingly similar in both groups before macrolide therapy . Long-term treatment with macrolides improved clinical symptoms, PaO(2), and forced expiratory volume in 1s (FEV(1)) equally in both groups . This study indicates that genetic susceptibility may not explain the pathogenesis of DPB, and that low-dose macrolide therapy can achieve clinical improvement irrespective of genetic predisposition in DPB. Gan To Kagaku Ryoho, 2004 Oct, 31(11), 1819 - 21 {A case of radiofrequency ablation therapy for recurrent hepatomas with tumor fever--efficacy of hepatic arterial infusion therapy with antibiotics and anticancer drugs}; Uchida S et al.; Efficacy of hepatic arterial infusion therapy (HAI) using antibiotics for hepatic abscess has been reported . However, we effectively performed RFA therapy after HAI with antibiotics and anticancer drugs for recurrent hepatomas with tumor fever . A 67-year-old female of recurrent hepatomas with fever is presented here . She was diagnosed with a 6 cm recurrent hepatoma, both in the right and IM lobes . Her liver function was child A with hepatitis C . On her CT scan, we found an enhanced 60 mm mass at an early phase and it was washed out at a delayed phase . Initially, we gave systemic medication of antibiotics, but could not decrease the fever . Therefore, we performed HAI with antibiotics and anticancer drugs . The patient's temperature went down after 14 days, and we were able to cut down her tumor size . After HAI, we were able to completely perform RFA for recurrent hepatomas. J Chromatogr A, 2004 Oct 29, 1054(1-2), 359 - 63 Cold-temperature stability of five beta-lactam antibiotics in bovine milk and milk extracts prepared for liquid chromatography-electrospray ionization tandem mass spectrometry analysis; Riediker S et al.; The stability of five major beta-lactam antibiotics (amoxicillin, ampicillin, cloxacillin, oxacillin, and penicillin G) in fortified milk and in milk extracts prepared for LC-ESIMS/MS analysis was studied at varying cold temperatures (4, -20, and -76 degrees C) . Storage of milk samples at 4 degrees C resulted in measurable losses of all beta-lactams after 6 days (>50% in most cases) . Slow degradation of penicillin G, cloxacillin, and oxacillin was observed in milk stored at -20 degrees C, but no losses were recorded at -76 degrees C over 4 weeks . All antibiotics showed good stability at all temperature tested in milk extracts prepared for LC-ESIMS/MS analysis . The results of this study emphasize adherence to adequate sample handling and storage protocols as to reflect residue levels at the time of sample submission. Nippon Rinsho, 2004 Nov, 62(11), 2101 - 7 {Continuous regional arterial infusion of protease inhibitor and antibiotic for severe acute pancreatitis}; Takeda K; Continuous regional arterial infusion (CRAI) of protease inhibitor and antibiotic has been established as an initial treatment for severe acute pancreatitis in Japan . CRAI therapy reduced the mortality rate and the frequency of infected pancreatic necrosis . Recently vasospasm has been recognized to be involved in the development of pancreatic ischemia or hypoperfusion in the early phase of the disease, and early application of CRAI of nafamostat may protect the evolution of ischemia into necrosis by inhibition of the increase in the intravascular coagulant activity. Clin Orthop, 2004 Oct, (427), 101 - 6 Alternative materials to acrylic bone cement for delivery of depot antibiotics in orthopaedic infections; McLaren AC; Acrylic bone cement has considerable laboratory and clinical data validating it as a delivery material for depot administration of antibiotics . However, an alternate material that does not require a secondary procedure for removal is desired . Many biodegradable materials have been evaluated as alternatives including protein-based materials (collagen, fibrin, thrombin, clotted blood), bone-graft, bone-graft substitutes and extenders (hydroxyapatite, beta-tricalcium phosphate, calcium sulfate, bioglass), and synthetic polymers (polyhanhydride, polylactide, polyglycolide, polyhydroxybutyrate-co-hydroxyvalerate, polyhydroxyalkanoate) . Various forms and combinations of these materials have been investigated worldwide, characterizing their elution properties and performance in treating osteomyelitis in animal models . Many of these have had limited clinical evaluation . Outside the United States, some of these materials are used clinically . In the United States, none have been approved . None are commercially available for clinical use . Morselized cancellous bone and calcium sulfate are the two materials that have been used clinically in the United States on a physician-prescribed, hand-mixed, basis . Considering the limited clinical data that currently are available, the use of these materials still is experimental . Clinical application should be cautious, limiting the total antibiotic load . Until definitive data are available, a prudent dose would be no higher than one that would have acceptable toxicity risk if administered intravenously over 24 hours. Clin Orthop, 2004 Oct, (427), 86 - 93 Local antibiotic therapy in the treatment of open fractures and osteomyelitis; Zalavras CG et al.; Local antibiotic therapy is part of the treatment protocol of open fractures and osteomyelitis . However, there are limitations in the literature evaluating the efficacy of the technique and controversies remain . Polymethylmethacrylate cement commonly is used as a delivery vehicle, but bioabsorbable vehicles are being investigated . The vehicle is impregnated with antibiotic(s) active against the suspected pathogens, usually an aminoglycoside and/or vancomycin . Elution depends on the surface area, the characteristics and permeability of the delivery vehicle, type and concentration of the antibiotic(s) used, presence of fluid, rate of fluid turnover, and time postimplantation . Local antibiotic therapy is a safe technique resulting in high local concentration of antibiotics with minimal systemic levels . Local antibiotics effectively have controlled infection in animal models and, despite limitations of the existing literature, seem to be useful in the clinical setting . The length of implantation and the need for removal of the delivery vehicle remain controversial . Nonabsorbable vehicles may eliminate the need for reoperation and removal. Clin Orthop, 2004 Oct, (427), 79 - 85 Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements; Hanssen AD et al.; The use of antibiotic-loaded bone cement is an accepted treatment method for infected joint arthroplasties . It is helpful to separate the use of antibiotic-loaded bone cement as a method of prophylaxis as compared with the treatment of an established infection . A low dose of antibiotic-loaded bone cement (< or = 1 g of antibiotic per batch of cement) should be used for prophylaxis, and high-dose antibiotic-loaded bone cement (> 1 g antibiotic per batch of cement) is indicated for treatment . The only commercially available antibiotic-loaded bone cement products are low dose, with the use of tobramycin or gentamicin as an antibiotic selection . High-dose antibiotic-loaded bone cement requires hand mixing by the surgeon to facilitate the use of high dosages and choices of multiple antibiotics . Treatment of infected hip and knee arthroplasties with high-dose antibiotic-loaded bone cement is aided by the use of spacers of various shapes and sizes . These spacers, whether they are static or articulating (mobile), are meant to provide local delivery of antibiotics, stabilization of soft tissues, facilitation of an easier reimplantation, and improved clinical outcomes. Clin Orthop, 2004 Oct, (427), 47 - 51 Systemic safety of high-dose antibiotic-loaded cement spacers after resection of an infected total knee arthroplasty; Springer BD et al.; The purpose of this study was to assess the systemic safety and potential adverse effects of using a high-dose antibiotic-impregnated cement spacer after resection arthroplasty of an infected total knee replacement . Between October 2000 and December 2002, 36 knees (34 patients) had a resection arthroplasty of an infected total knee prosthesis with placement of a high-dose antibiotic impregnated cement spacer . There were 24 men and 10 women with a mean age of 66.5 years (range, 48-84 years) . All spacers placed contained an average of 3.4 batches of cement with an average total dose of 10.5 g of vancomycin (range, 3-16 g) and 12.5 g of gentamicin (range, 3.6-19.2 g) . All patients were followed up post-operatively until reimplantation for evidence of renal failure . The preoperative creatinine ranged from 0.7 to 1.8 mg/dL . All patients were concomitantly treated with 6 weeks of intravenous organism-specific antibiotics . One patient with normal preoperative renal function (Cr 0.7 mg/dL) had a perioperative 1-day transient rise in serum creatinine (1.7 mg/dL) postoperatively that subsequently normalized . No patients showed any clinical evidence of acute renal insufficiency, failure, or other systemic side effects of the antibiotics . Treatment of patients with an infected total knee arthroplasty with high-dose vancomycin and gentamicin antibiotic spacers seems to be clinically safe. Clin Orthop, 2004 Oct, (427), 37 - 46 Successful treatment of total hip and knee infection with articulating antibiotic components: a modified treatment method; Evans RP; There are many problems associated with the use of articulating antibiotic cement spacer blocks and articulating components in the two-stage treatment of total hip replacement and total knee replacement infections . These include loss of motion during and after treatment, bone loss, generation of cement debris, inadequate dosing of cement with the appropriate antibiotic, and biologic failure . Forty-four patients with 54 consecutive periprosthetic hip and knee infections (31 septic total knee arthroplasties and 23 septic total hip arthroplasties) had treatment with a modified two-stage reimplantation protocol using articulating components made of antibiotic-cement-only prosthetic components and antibiotic-cement-covered prosthetic components between January 1995 and May 2002 . Second-stage revision, after six weeks of parenteral antibiotics, was completed an average of 84 days after the first stage . A minimum two-year followup after final treatment is evaluated . One of the 23 total hip replacement infections persisted or recurred with the original organism(s) after treatment (95.7% success) as did two of the 31 total knee replacement infections (93.5% success) . Combined success rate was 94.4% . This modified treatment method incorporates early range of motion during first-stage treatment with articulating components that provide local high-dose elution of broad-spectrum antibiotics, provides the flexibility of customizing the antibiotic cement components with culture-directed antibiotics, and results in a high biologic success rate. J Neurosci, 2004 Nov 17, 24(46), 10335 - 42 Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease; Ferrante RJ et al.; Huntington's disease (HD) is a fully penetrant autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in the Huntingtin gene . Transcriptional dysfunction, excitotoxicity, and oxidative stress have all been proposed to play important roles in the pathogenesis of HD . This study was designed to explore the therapeutic potential of mithramycin, a clinically approved guanosine-cytosine-rich DNA binding antitumor antibiotic . Pharmacological treatment of a transgenic mouse model of HD (R6/2) with mithramycin extended survival by 29.1%, greater than any single agent reported to date . Increased survival was accompanied by improved motor performance and markedly delayed neuropathological sequelae . To identify the functional mechanism for the salubrious effects of mithramycin, we examined transcriptional dysfunction in R6/2 mice . Consistent with transcriptional repression playing a role in the pathogenesis of HD, we found increased methylation of lysine 9 in histone H3, a well established mechanism of gene silencing . Mithramycin treatment prevented the increase in H3 methylation observed in R6/2 mice, suggesting that the enhanced survival and neuroprotection might be attributable to the alleviation of repressed gene expression vital to neuronal function and survival . Because it is Food and Drug Administration-approved, mithramycin is a promising drug for the treatment of HD. Am J Obstet Gynecol, 2004 Nov, 191(5), 1661 - 5 Prophylactic antibiotics for non-laboring patients with intact membranes undergoing cesarean delivery: an economic analysis; Chelmow D et al.; OBJECTIVE: We conducted an economic analysis of prophylactic antibiotic administration for elective cesarean delivery . STUDY DESIGN: We created a decision tree comparing the use of prophylactic antibiotics (cefazolin 1 gm intravenous) with no antibiotic use . We modeled the potential for anaphylaxis, and included outcomes of fever and endometritis . Outcome probabilities and effectiveness of antibiotic administration were derived from published sources . Costs are 2001 estimates derived from our hospital's accounting system . Sensitivity analyses were performed over the range of actual patient costs and 95% CI of the risk and probability estimates . RESULTS: Cost of an uncomplicated elective cesarean delivery was $1638.57 . Fever evaluation added $125.91 . Elective procedure complicated by endometritis cost $2327.29 . Cefazolin administration cost $1.01 . The following estimates were used: relative risk (RR) of endometritis with antibiotics was 0.18 (95% CI 0.07-0.45), fever 0.47 (95% CI 0.32-0.68), risk of endometritis without prophylaxis 4.8% (95% CI 0.9%-43%), and fever without prophylaxis 14.4% (95% CI 4%-33%) . Cost of an average case without prophylaxis was $1683.72; prophylaxis reduced this to $1653.06 . Sensitivity analysis over the ranges above still yielded cost savings . CONCLUSION: Administration of prophylactic antibiotics for elective cesarean delivery reduced costs by $30.66 per case, approximately 2% of the total cost . Prophylactic antibiotic administration results in cost savings for elective cesarean delivery. Clin Orthop, 2004 Oct, 1(427), 101 - 106 Alternative Materials to Acrylic Bone Cement for Delivery of Depot Antibiotics in Orthopaedic Infections; McLaren AC; Acrylic bone cement has considerable laboratory and clinical data validating it as a delivery material for depot administration of antibiotics . However, an alternate material that does not require a secondary procedure for removal is desired . Many biodegradable materials have been evaluated as alternatives including protein-based materials (collagen, fibrin, thrombin, clotted blood), bone-graft, bone-graft substitutes and extenders (hydroxyapatite, beta-tricalcium phosphate, calcium sulfate, bioglass), and synthetic polymers (polyhanhydride, polylactide, polyglycolide, polyhydroxybutyrate-co-hydroxyvalerate, polyhydroxyalkanoate) . Various forms and combinations of these materials have been investigated worldwide, characterizing their elution properties and performance in treating osteomyelitis in animal models . Many of these have had limited clinical evaluation . Outside the United States, some of these materials are used clinically . In the United States, none have been approved . None are commercially available for clinical use . Morselized cancellous bone and calcium sulfate are the two materials that have been used clinically in the United States on a physician-prescribed, hand-mixed, basis . Considering the limited clinical data that currently are available, the use of these materials still is experimental . Clinical application should be cautious, limiting the total antibiotic load . Until definitive data are available, a prudent dose would be no higher than one that would have acceptable toxicity risk if administered intravenously over 24 hours. Clin Orthop, 2004 Oct, 1(427), 86 - 93 Local Antibiotic Therapy in the Treatment of Open Fractures and Osteomyelitis; Zalavras CG et al.; Local antibiotic therapy is part of the treatment protocol of open fractures and osteomyelitis . However, there are limitations in the literature evaluating the efficacy of the technique and controversies remain . Polymethylmethacrylate cement commonly is used as a delivery vehicle, but bioabsorbable vehicles are being investigated . The vehicle is impregnated with antibiotic(s) active against the suspected pathogens, usually an aminoglycoside and/or vancomycin . Elution depends on the surface area, the characteristics and permeability of the delivery vehicle, type and concentration of the antibiotic(s) used, presence of fluid, rate of fluid turnover, and time postimplantation . Local antibiotic therapy is a safe technique resulting in high local concentration of antibiotics with minimal systemic levels . Local antibiotics effectively have controlled infection in animal models and, despite limitations of the existing literature, seem to be useful in the clinical setting . The length of implantation and the need for removal of the delivery vehicle remain controversial . Nonabsorbable vehicles may eliminate the need for reoperation and removal. Clin Orthop, 2004 Oct, 1(427), 79 - 85 Practical Applications of Antibiotic-Loaded Bone Cement for Treatment of Infected Joint Replacements; Hanssen AD et al.; The use of antibiotic-loaded bone cement is an accepted treatment method for infected joint arthroplasties . It is helpful to separate the use of antibiotic-loaded bone cement as a method of prophylaxis as compared with the treatment of an established infection . A low dose of antibiotic-loaded bone cement (</= 1 g of antibiotic per batch of cement) should be used for prophylaxis, and high-dose antibiotic-loaded bone cement (> 1 g antibiotic per batch of cement) is indicated for treatment . The only commercially available antibiotic-loaded bone cement products are low dose, with the use of tobramycin or gentamicin as an antibiotic selection . High-dose antibiotic-loaded bone cement requires hand mixing by the surgeon to facilitate the use of high dosages and choices of multiple antibiotics . Treatment of infected hip and knee arthroplasties with high-dose antibiotic-loaded bone cement is aided by the use of spacers of various shapes and sizes . These spacers, whether they are static or articulating (mobile), are meant to provide local delivery of antibiotics, stabilization of soft tissues, facilitation of an easier reimplantation, and improved clinical outcomes. Clin Orthop, 2004 Oct, 1(427), 47 - 51 Systemic Safety of High-Dose Antibiotic-Loaded Cement Spacers after Resection of an Infected Total Knee Arthroplasty; Springer BD et al.; The purpose of this study was to assess the systemic safety and potential adverse effects of using a high-dose antibiotic-impregnated cement spacer after resection arthroplasty of an infected total knee replacement . Between October 2000 and December 2002, 36 knees (34 patients) had a resection arthroplasty of an infected total knee prosthesis with placement of a high-dose antibiotic impregnated cement spacer . There were 24 men and 10 women with a mean age of 66.5 years (range, 48-84 years) . All spacers placed contained an average of 3.4 batches of cement with an average total dose of 10.5 g of vancomycin (range, 3-16 g) and 12.5 g of gentamicin (range, 3.6-19.2 g) . All patients were followed up postoperatively until reimplantation for evidence of renal failure . The preoperative creatinine ranged from 0.7 to 1.8 mg/dL . All patients were concomitantly treated with 6 weeks of intravenous organism-specific antibiotics . One patient with normal preoperative renal function (Cr 0.7 mg/dL) had a perioperative 1-day transient rise in serum creatinine (1.7 mg/dL) postoperatively that subsequently normalized . No patients showed any clinical evidence of acute renal insufficiency, failure, or other systemic side effects of the antibiotics . Treatment of patients with an infected total knee arthroplasty with high-dose vancomycin and gentamicin antibiotic spacers seems to be clinically safe. Clin Orthop, 2004 Oct, 1(427), 37 - 46 Successful Treatment of Total Hip and Knee Infection with Articulating Antibiotic Components: A Modified Treatment Method; Evans RP; There are many problems associated with the use of articulating antibiotic cement spacer blocks and articulating components in the two-stage treatment of total hip replacement and total knee replacement infections . These include loss of motion during and after treatment, bone loss, generation of cement debris, inadequate dosing of cement with the appropriate antibiotic, and biologic failure . Forty-four patients with 54 consecutive periprosthetic hip and knee infections (31 septic total knee arthroplasties and 23 septic total hip arthroplasties) had treatment with a modified two-stage reimplantation protocol using articulating components made of antibiotic-cement-only prosthetic components and antibiotic-cement-covered prosthetic components between January 1995 and May 2002 . Second-stage revision, after six weeks of parenteral antibiotics, was completed an average of 84 days after the first stage . A minimum two-year followup after final treatment is evaluated . One of the 23 total hip replacement infections persisted or recurred with the original organism(s) after treatment (95.7% success) as did two of the 31 total knee replacement infections (93.5% success) . Combined success rate was 94.4% . This modified treatment method incorporates early range of motion during first-stage treatment with articulating components that provide local high-dose elution of broad-spectrum antibiotics, provides the flexibility of customizing the antibiotic cement components with culture-directed antibiotics, and results in a high biologic success rate. J Antimicrob Chemother, 2004 Dec, 54(6), 1116 - 21 Epub 2004 Nov 16. Antibiotic prescribing for respiratory tract infections in Dutch primary care in relation to patient age and clinical entities; Akkerman AE et al.; OBJECTIVES: To obtain detailed information on current prescribing rates of antibiotics for respiratory tract infections (RTIs) in Dutch general practice and its relation with age and respiratory tract clinical entities . METHODS: We assessed the mean proportion of antibiotics prescribed for RTIs per age group, contact-based and population-based using all patient contacts concerning RTIs in the year 2000 selected from the IPCI database, containing information on general practice consultations of 235 290 patients . RESULTS: In one-third of all contacts concerning RTIs, antibiotics were prescribed, with much variation between age groups and clinical entities . For children (0-15 years) and the elderly (over 75 years), the lowest contact-based percentages of prescribed antibiotics for RTIs were found, while population-based, children of age 0-5 years received far more antibiotics for RTIs . High prescribing rates were seen in patients with sinusitis-like complaints (67%) or pneumonia (78%), whereas low rates were found for patients with upper RTIs (16%) . CONCLUSIONS: Potential over-prescribing of antibiotics for RTIs occurs in the age group 31-65 years, not in children and the elderly, and in patients with upper RTIs, sinusitis and most likely acute bronchitis (contact-based) . The management of these subgroups of patients should be addressed in quality assurance programmes . Children and the elderly visit the GP much more often than adults, which can be explained by more frequent (children) or more severe (elderly) RTI morbidity, but in proportion they do not receive more antibiotics. Z Naturforsch {C}, 2004 Sep-Oct, 59(9-10), 739 - 48 Interactions of novel morpholine and hexamethylene derivatives of anthracycline antibiotics with DNA; Piestrzeniewicz MK et al.; Doxorubicin (DOX), daunorubicin (DRB), epidoxorubicin (EDOX) and their analogues with a 3'-NH2 group in daunosamine form a covalent bond with a 2-NH2 group of guanine via a methylene group from formaldehyde (CH2O) . It is assumed that a Schiff base type intermediate is formed between CH2O and the 3'-NH2 group in the reaction . This reaction is supposed to occur in the cell . New analogues of anthracyclines with formamidine functionality bound to C-3' of daunosamine and containing the bulky morpholine (DRBM, DOXM and EDOXM) or hexamethyleneimine rings attached are studied in our laboratory . These substituents decrease the association of the drugs to DNA and potentially hinder the formation of Schiff base-intermediates . Our experiments indicate that the formation of the covalent complexes by DRB, DOX and EDOX under these conditions is confirmed by a high enhancement (17-40x) of the inhibition of overall RNA synthesis by E . coli RNA polymerase on T7 DNA . DRBM and DOXM exhibit a lower enhancement of the inhibition by CH2O (7-13x) . The other analogues show a 1.6-3x increase of inhibition . Hence, their covalent binding is lower than that of the parent compounds . These conclusions are confirmed by spectrophotometric estimations following removal of non-covalently associated drugs . Electrophoretic analysis of drug-DNA complexes formed in the presence of CH2O indicates that DRBM and DOXM as their parent compounds induce labile cross-links in DNA . Comparison of the results obtained at the subcellular level with cytotoxicity estimations indicates that there is a correlation between cytotoxicity of the anthracyclines on L1210 cells and transcriptional template activity of drug-DNA complexes formed in the presence of CH2O (r = 0.64; n = 9) . These data confirm a notion that covalent attachment of anthracyclines to DNA is an essential event leading to cytotoxicity. Jpn J Antibiot, 2004 Aug, 57(4), 413 - 9 {Development of software for data analysis by therapeutic drug monitoring of teicoplanin, a glycopeptide antibiotic}; Niwa T et al.; We developed a new software named TEICTDM based on the Bayesian estimation utilized in the therapeutic drug monitoring (TDM) of teicoplanin, a glycopeptide antibiotic, for the estimation of individual pharmacokinetic parameters . Therefore, it is necessary to input more than one plasma concentration(s) determined in individual patient . Individual pharmacokinetic parameters were calculated by a least squares methods, MULTI2 (BAYES) . Two-compartment model was applied to determine individual pharmacokinetic parameters in male healthy volunteers in Japan, and the relationship between clearance of teicoplanin and creatinine clearance in adult patients with various degrees of renal impairment in Europe was used . A series of work from data input to graph drawing or printing of results could efficiently carried out with the best of use of this software, suggesting that this software is now available in clinical practice. Pharmacoepidemiol Drug Saf, 2005 Jan, 14(1), 53 - 9 Evaluation of an antibiotic intravenous to oral sequential therapy program; Pablos AI et al.; AIM: This study was designed to analyse the drug consumption difference and economic impact of an antibiotic sequential therapy focused on quinolones . METHOD: We studied the consumption of quinolones (ofloxacin/levofloxacin and ciprofloxacin) 6 months before and after the implementation of a sequential therapy program in hospitalised patients . It was calculated for each antibiotic, in its oral and intravenous forms, in defined daily dose (DDD/100 stays per day) and economical terms (drug acquisition cost) . At the beginning of the program ofloxacin was replaced by levofloxacin and, since their clinical uses are similar, the consumption of both drugs was compared during the period . RESULTS: In economic terms, the consumption of intravenous quinolones decreased 60% whereas the consumption of oral quinolones increased 66% . In DDD/100 stays per day, intravenous forms consumption decreased 53% and oral forms consumption increased 36% . CONCLUSIONS: Focusing on quinolones, the implementation of a sequential therapy program based on promoting an early switch from intravenous to oral regimen has proved its capacity to alter the utilisation profile of these antibiotics . The program has permitted the hospital a global saving of $41 420 for these drugs during the period of time considered . Copyright (c) 2004 John Wiley & Sons, Ltd. J Chromatogr A, 2004 Oct 8, 1051(1-2), 247 - 52 Use of a hepta-Tyr antibiotic modified silica stationary phase for the enantiomeric resolution of D,L-loxiglumide by electrochromatography and nano-liquid chromatography; Fanali S et al.; Hepta-Tyr antibiotic modified silica stationary phase was used for the chiral resolution of D,L-loxiglumide, a new drug under investigation proposed for the treatment of gastrointestinal diseases . The chiral stationary phase was packed into fused silica capillaries of 75 microm i.d . for a length of only 7 cm and used for both capillary electrochromatography (CEC) and nano-liquid chromatography (nano-LC) running the experiments with the same instrumentation; in order to increase the electroosmotic flow (EOF) the antibiotic stationary phase was mixed with amino-silica particles (3:1, w/w) generating a relatively high reversed EOF . The enantiomeric resolution of loxiglumide by CEC was strongly influenced by several experimental parameters such as applied electric field, mobile phase composition, capillary temperature, etc . Optimum experimental conditions were found applying 15 kV at 20 degrees C and eluting with acetonitrile-sodium phosphate buffer at pH 6 (1:1, v/v) . The same capillary was tested for nano-LC experiments . Good chiral separation of loxiglumide was achieved selecting the appropriate mobile phase considering the type and concentration of organic modifier . The nano-LC optimised method was therefore validated and applied to the analysis of a pharmaceutical formulation declared to contain only D-loxiglumide. Stat Med, 2005 Jan 15, 24(1), 1 - 10 A comparison of intent-to-treat and per-protocol results in antibiotic non-inferiority trials; Brittain E et al.; While the intent-to-treat (ITT) analysis is widely accepted for superiority trials, there remains debate about its role in non-inferiority trials . It is often said that the ITT tends to be anti-conservative in the demonstration of non-inferiority . This concern has led to some reliance on per-protocol (PP) analyses that exclude patients on the basis of post-baseline events, despite the inherent bias of such analyses . We compare ITT and PP results from antibiotic trials presented to the public at the FDA's Anti-infective Drug Advisory Committee from 1999 to 2003 . While the number of available trials is too small to produce clear conclusions, these data did not support the assumption that the ITT would lead to smaller treatment difference than the PP, in the setting of antibiotic trials . Possible explanations are discussed . Published in 2004 by John Wiley & Sons, Ltd. Am Surg, 2004 Oct, 70(10), 858 - 62 The efficacy of postoperative oral antibiotics in appendicitis: a randomized prospective double-blinded study; Taylor E et al.; The conventional treatment of acute appendicitis is appendectomy followed by intravenous (IV) antibiotics until intraabdominal infection has resolved . It is controversial as to whether it is efficacious to add a course of oral antibiotics after cessation of IV antibiotics . All consenting patients who presented to Kern Medical Center between October 2000 and June 2003 with acute appendicitis were entered into the study . Perforated/gangrenous appendicitis was equally represented in the two study arms . After appendectomy, and when IV antibiotics were ready to be discontinued, patients were randomized to receive a 7-day outpatient course of either placebo (Group 1) or oral antibiotics (Group 2) . Patients were monitored for infectious complications for a minimum of 3 months, and there was no statistical difference (11.5% in Group 1 vs 12.1% in Group 2, P = 0.61) . The data suggest that adding a course of outpatient oral antibiotics, after completing a course of IV antibiotics, does not decrease postoperative infectious complications in appendicitis patients. Respir Med, 2004 Nov, 98(11), 1093 - 101 Antibiotic prescribing rates in the US ambulatory care setting for patients diagnosed with influenza, 1997-2001; Ciesla G et al.; To document the rate and cost of antibiotic prescribing for patients diagnosed only with influenza during US ambulatory care visits . Federal survey data for 1997-2001 were used to estimate outpatient trends for all patients and healthy people age 5-49 years . Cost estimates were based on Medicare payments and Red Book average wholesale prices in 2003 . Antibiotic prescribing for influenza is widespread; 38% of visits led to an antibiotic prescription of which one-third were for broad spectrum antibiotics . Inappropriate antibiotics cost dollar 18.5 million annually and may contribute to resistance . Increased vaccination rates and viral testing could reduce these trends. Org Lett, 2004 Nov 11, 6(23), 4273 - 5 DFT study of pericyclic reaction cascades in the synthesis of antibiotic TAN-1085; Akerling ZR et al.; DFT calculations show that aromatic and bis-methoxy substituent effects in a synthetic precursor of TAN-1085 strongly favor a {1,7} sigmatropic hydrogen shift over the 6 pi electrocyclic pathway, rendering the latter unfavorable in synthesis. Genetika, 2004 Aug, 40(8), 1063 - 7 The induction of chromosomal aberrations by tetra antibiotic in bone marrow cells of rats in vivo; Cakmak T et al.; The aim of this study was to investigate the in vivo effects of Tetra (Tetralet) antibiotic on the chromosomal aberrations (CA) in bone marrow cells of rats (Rattus norvegicus var . albinos) . Tetra antibiotic significantly increased the percentage of abnormal cells and the chromosomal aberrations per cells (CA/cell) in bone marrow cells of rats at concentrations of 100 and 200 mg/kg body weight for 12 and 24 hours treatment periods for each . In addition, the percentage of abnormal cells and the CA/cell increased dose-dependently for 12 hours treatment period; In contrast, mitotic index (MI) was decreased when compared with negative control and solvent controls for 12 hours treatment period . However, MI increased depend on Tetra antibiotic dose for 24 hour treatment period. Indian Pediatr, 2004 Oct 7, 41(10), 1045 - 1048 Non-antibiotic Associated C . diffcile Diarrhea in a 7 week-old Infant; Kader A et al.; We describe a rare case of non-antibiotic associated severe C . difficile diarrhea in a 7-week-old boy . He had massive fluid loss and electrolyte imbalance . He required total parentral nutrition for 10 days and eventually recovered with oral metronidazole . Most of the reported cases in literature are associated with prior antibiotic exposure or in hospitalized patients. J Pharm Biomed Anal, 2004 Nov 15, 36(3), 593 - 600 Acid catalysed degradation of some spiramycin derivatives found in the antibiotic bitespiramycin; Shi X et al.; Bitespiramycin is a novel antibiotic containing a number of 4''-acylated spiramycin derivatives (isovalerylspiramycins I-III, butanoylspiramycin III, propanoylspiramycin III and acetylspiramycin III) as major components . These spiramycin derivatives are susceptible to degradation in acid solution . Liquid chromatography-ion trap mass spectrometry (LC/MS(n)) was used to study the degradation of these spiramycin derivatives in simulated gastric fluid at 37 degrees C . All derivatives degraded by first-order reactions for which rate constants (k) and half-lives (t(1/2)) were calculated . Acyl groups at position 3 had less effect on acid-stability of spiramycin derivatives than acyl groups at position 4'' . The introduction of 4''-acyl groups enhanced the acid-stability of spiramycin derivatives and altered the degradation pathway in simulated gastric fluid such that loss of forosamine rather than loss of mycarose becomes the major degradation pathway. J Pharm Biomed Anal, 2004 Nov 15, 36(3), 483 - 90 Molecularly imprinted solid phase extraction-pulsed elution-mass spectrometry for determination of cephalexin and alpha-aminocephalosporin antibiotics in human serum; Wu SG et al.; A highly selective molecularly imprinted solid phase extraction (MISPE)-pulsed elution (PE) method coupled with electrospray mass spectrometry (MS) was developed for the rapid screening and determination of cephalexin in alpha-aminocephalosporin antibiotics . This method involved the solid phase extraction of cephalexin using a molecularly imprinted polymer micro-column, and pulsed elution with 1% trifluoroacetic acid in methanol, which contains sulindac as an internal standard for enhanced precision in MS detection . An LC/MS spectrometer was operated in the positive electrospray mode, and the selected-ion-recording (SIR) function was employed to detect the molecular ions of cephalexin, cefradine, cefadroxil and sulindac at m/z 348, 350, 363 and 357 . Linearity was achieved in the cephalexin concentration range from 0.3 to 25microg/ml (or 5-500ng) (R(2) = 0.998) . The detection limit was estimated at 0.04microg/ml (or 0.8ng) of cephalexin . Advantages of the newly developed MISPE-PE-MS, over the previously reported MISPE-DPE-FPE-UV, were evidenced in terms of detection limit, analysis time, solvent consumption, and simplicity of method development. J Inorg Biochem, 2004 Nov, 98(11), 1795 - 805 Spectroscopic studies on the anticancer antibiotic Altromycin H and the interaction with copper(II) ions; Menidiatis C et al.; The antitumor antibiotic Altromycin H was studied using electronic absorption (UV-Vis.) and circular dichroism (CD) spectroscopy . The dissociation constants of the phenolic groups on C(5) and C(11) were estimated as pK(1)=6.7 and pK(2)=11.8 at 25 degrees C, respectively, and a complete assignment of the CD and UV-Vis . bands is proposed . The interaction of Cu(II) ions with the Altromycin H has been also investigated by UV-Vis., CD and electron paramagnetic resonance (EPR) spectroscopy . A pH depended stepwise complex formation was observed . At pH<4 no copper-Altromycin H interactions were detected . At the 4<pH<8 the Cu(II) ions coordinate to Altromycin H via the C(4)O and C(5)OH groups atoms of the chromophore ring and the {Cu(AltroH)(2)} complex (formation constant, K(f), 4.00+/-0.9 x 10(11) M(-2) at 25 degrees C) is the predominant species . In alkaline solution the hydroxo-bridged complex, {Cu(OH)(AltroH)}(2), is proposed to be as the unique present species. Br J Clin Pharmacol, 2004 Nov, 58(5), 521 - 7 Comparison of gentamicin dose estimates derived from manual calculations, the Australian 'Therapeutic Guidelines: Antibiotic' nomogram and the SeBA-GEN and DoseCalc software programs; Mohan M et al.; AIM: To compare gentamicin dose estimates from four predictive methods . METHODS: A retrospective study was conducted, comprising patients at Fremantle Hospital who received gentamicin therapy and had at least one gentamicin serum concentration reported . A manual calculation method, the Australian 'Therapeutic Guidelines: Antibiotic' (TGA) nomogram and the SeBA-GEN and DoseCalc software packages were compared . SeBA-GEN dose estimates were regarded as the reference standard . RESULTS: There were 64 males and 30 females with mean age of 58 +/- 16 years . In patients with moderate renal impairment (CL(Cr) = 30-60 ml min(-1); n = 21), mean dose estimates using DoseCalc and the manual calculation method were comparable to SeBA-GEN but the mean TGA nomogram dose (230 mg; 95% confidence interval 179, 281) was significantly lower than SeBA-GEN (286 mg; 261, 311; P = 0.002; one-way RM anova) . In patients with mild renal impairment (CL(Cr) = 60-90 ml min(-1); n = 48), DoseCalc (392 mg; 367, 427) was comparable to SeBA-GEN (377 mg; 362, 392) . Although the manual method (341 mg; 306, 376; P = 0.007) and the TGA nomogram (335 mg; 302, 368; P < 0.001) estimates were significantly lower than SeBA-GEN, the practical difference was modest . CONCLUSIONS: SeBA-GEN and DoseCalc are generally comparable for estimation of gentamicin doses in patients with renal impairment . The 'Therapeutic Guidelines: Antibiotic' nomogram is a valid approach to dosage estimation, but only when used in patients with normal renal function . Simple manual calculations are a suitable alternative in patients with renal impairment. Pediatrics, 2004 Nov, 114(5), 1206 - 11 Increased use of second-generation macrolide antibiotics for children in nine health plans in the United States; Stille CJ et al.; BACKGROUND: Widespread use of broad-spectrum antibiotics contributes to increasing rates of bacterial resistance to antibiotics . Second-generation macrolides have become popular for use among children because of their broad spectrum and favorable dosing and side-effect profiles, although experts do not generally recommend them for use as initial treatment of infections among younger children . OBJECTIVE: To assess trends in second-generation macrolide use from 1996 to 2000 among children treated as outpatients in 9 US health plans, including associated diagnoses and use as initial treatment . METHODS: We sampled claims data for 25000 children, 3 months to <18 years of age, who were enrolled between September 1, 1995, and August 31, 2000, in each of 9 US health plans . Medications dispensed were linked with ambulatory visit claims to assign diagnoses . Dispensings without another antibiotic dispensing recorded in the previous 42 days were analyzed as initial treatment of a new illness episode . We analyzed trends in prescribing overall, for initial therapy, and, within specific diagnoses, for differences among health plans . RESULTS: From 1995-1996 to 1999-2000, although overall antibiotic use decreased from 1.15 to 0.91 dispensings per person-year, second-generation macrolide use increased from 0.022 to 0.063 dispensings per person-year . Use as a proportion of all antibiotic dispensings increased from 1.9% to 6.9%, and use as initial therapy increased from 1.4% to 6% . For children <6 years of age, second-generation macrolide use as initial therapy increased from 0.9% to 5.0% for otitis media and from 5.2% to 24.0% for pneumonia . There was a wide range of prescribing rates among health plans during the last year of the study, from 0.006 to 0.135 dispensings per person-year . CONCLUSIONS: Despite recent trends toward decreased antibiotic use among children, the use of second-generation macrolides among children has increased dramatically, even among younger children, for whom use for initial treatment of illness is not recommended . Large differences in prescribing rates exist among health plans . Continued efforts to promote the use of narrower-spectrum agents when appropriate are needed. Int J Antimicrob Agents, 2004 Nov, 24(5), 473 - 8 Outpatient parenteral antibiotic therapy (OPAT) in different countries: a comparison; Esposito S et al.; In order to assess how outpatient parenteral antibiotic therapy (OPAT) is managed in different countries, we analyzed the data collected in the USA, UK and Italy by the International OPAT Registry using an ad hoc Access/Excel Microsoft program . The analysis of data concerned 9826 patients in the USA, 981 in the UK and 620 in Italy . Differences were observed in several aspects of OPAT management such as the infections treated and the antibiotics utilized . The duration of therapy also differed: it was much longer in Italy (56.0 average days), than in the USA (22.5 days) and UK (19.9 days) . Delivery model, delivery route and infusion devices show substantial differences . The present analysis shows that OPAT is carried out with substantial differences in different countries probably according to different programmes and guidelines adopted. Int J Antimicrob Agents, 2004 Nov, 24(5), 468 - 72 The effect of adsorption, filter material and point of dilution on antibiotic elimination by haemofiltration an in vitro study of levofloxacin; Choi G et al.; We studied an in vitro model of continuous venous-venous haemofiltration (CVVH), into which levofloxacin 100 mg was infused, to determine levofloxacin adsorption and to determine the effect of filter material and point of dilution (pre- or post-filter) on sieving coefficient . Mean (standard deviation; S.D.) adsorption was 18.7 (5.3) mg for the polyamide filter and 40.2 (2.0) mg for the polyacrylonitrile (PAN) filter (P < 0.001) . Post-dilution resulted in a minor, but statistically significant, decrease in sieving coefficient (pre-dilution 0.96 (S.D . 0.10), post-dilution 0.88 (S.D . 0.11) with the PAN filter . These data indicate that the variability in published values for levofloxacin sieving coefficient are not due to variation in point of dilution or membrane type (PAN or polyamide) . Significant adsorption of levofloxacin onto PAN filters occurs. Chemosphere, 2004 Dec, 57(10), 1479 - 88 Determination of antibiotic substances in hospital sewage water using solid phase extraction and liquid chromatography/mass spectrometry and group analogue internal standards; Lindberg R et al.; A method for determination of antibiotics in hospital sewage water has been developed and validated . Analogue internal standards for fluoroquinolones, sulfonamides, trimethoprim, beta-lactams (penicillins and cephalosporins), nitroimidazoles and tetracyclines were successfully used for calibration and shown to generally improve precision compared to external calibration . Matrix components caused ion suppression/enhancement effects during the MS detection for all analytes studied . Two effects were observed: general suppression and short-term variations in the MS response . In the hospital sewage water large temporal variations in the analyte concentration were observed during the course of the sampling period (seven grab samples in 13 h) . Analyte concentrations varied within the following ranges (in microg l(-1)): ciprofloxacin, 3.6-101.0; metronidazole, 0.1-90.2; sulfamethoxazole, 0.4-12.8; ofloxacin, 0.2-7.6; trimethoprim, 0.6-7.6; and doxycycline, 0.6-6.7. Hinyokika Kiyo, 2004 Sep, 50(9), 629 - 31 {A case of inflammatory pseudotumor of renal pelvis showing a complete response to antibiotics}; Sugimoto K et al.; A 20-year-old woman was admitted with chief complaints of high fever and right lumbago . Abdominal computed tomography (CT) and ultrasonography revealed a right renal pelvic tumor 25 mm in diameter . Although malignancy could not be confirmed by the scan, we administered antibiotics based on a diagnosis of inflammatory pseudotumor of the renal pelvis . After treatment, no tumor was detected . In such cases,because diagnosis is generally difficult, surgery is usually performed . However, in this case, the patient showed a complete response to antibiotics. Swiss Med Wkly, 2004 Aug 21, 134(33-34), 481 - 5 Antibiotic misuse in medium-sized Swiss hospitals; Bugnon-Reber A et al.; Antibiotics account for a substantial proportion of hospital drug expenditures and tend to be misused or overused, generating unnecessary costs and causing the emergence of resistant bacteria . Antibiotic use was evaluated in a one-day prevalence study performed on the surgical and medical wards of eight Swiss non-university hospitals . 173 of the 695 inpatients present (25%) were on antibiotics and 163 could be evaluated . 35 prescriptions were secondary to an infectious disease consultation . 60 of the remaining 128 (47%) were considered inappropriate, of which 17 (28%) lacked any indication for antibiotic use . The rates of misuse were higher in surgery than in medicine (58 vs . 34%; OR = 2.5 {95% CI: 1.1-5.9}), and higher for prophylaxis than for treatment (72 vs . 41%; OR = 4.1 {95% CI: 1.3-15.5}) . Savings of 545 euros (95% CI: from -116 to 1,206 euros) on the study day and 6,256 euros (95% CI: from -2,221 to 14,732 euros) for the total treatments or prophylaxis administered would have resulted from infectious disease consultations. Yakugaku Zasshi, 2004 Nov, 124(11), 815 - 24 {Comparison of the effects of prophylactic antibiotic therapy and cost-effectiveness between cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway}; Ise Y et al.; The present study was designed to investigate the effects of prophylactic antibiotic therapy and the cost-effectiveness of Cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway . 157 patients (62 in the CEZ group and 95 in the SBT/ABPC group), who underwent surgery for gastric cancer at the First Department of Surgery of our hospital, were investigated . There was no significant difference between the groups with regard to sex, age, incidence of complication, stage of cancer, surgical method, operative time and blood loss, length of hospitalization, the appearance of systemic inflammatory response syndrome (SIRS), changes body temperature, white blood cell count (WBC), C-reactive protein (CRP), or clinical outcome of postoperative care by a nurse during post-operation for 7 days . The prophylactic effect of infection was also no different between the CEZ (69.4%) and SBT/ABPC (69.5%) groups . In contrast, decision analysis strongly indicated that the anticipate cost of antibiotics was higher in the latter group (yen 20402) than in the CEZ group (yen 15556), suggesting that the prophylactic effect of CEZ may be more cost-effective . Thus, evaluations of pharmacotherapy from the aspect of cost may be one of the important responsibility of hospital pharmacists in the future. Obstet Gynecol, 2004 Nov, 104(5 Pt 1), 1051 - 7 Antibiotics for preterm rupture of the membranes: a systematic review; Kenyon S et al.; OBJECTIVE: We sought to evaluate the administration of antibiotics to pregnant women with preterm rupture of membranes (PROM) . DATA SOURCES: We collected data by using the Cochrane Controlled Trials Register and MEDLINE . METHODS OF STUDY SELECTION: We included randomized controlled comparisons of antibiotic versus placebo (14 trials, 6,559 women) . TABULATION, INTEGRATION, AND RESULTS: Antibiotics were associated with a statistically significant reduction in maternal infection and chorioamnionitis . There also was a reduction in the number of infants born within 48 hours and 7 days and with the following morbidities: neonatal infection (relative risk {RR} 0.67, 95% confidence interval {CI} 0.52-0.85), positive blood culture (RR 0.75, 95% CI 0.60-0.93), use of surfactant (RR 0.83 95% CI 0.72-0.96), oxygen therapy (RR 0.88, 95% CI 0.81-0.96), and abnormal cerebral ultrasound scan before discharge from hospital (RR 0.82, 95% CI 0.68-0.99) . Perinatal mortality was not significantly reduced (RR 0.91, 95% CI 0.75-1.11) . A benefit was present both in trials where penicillins and erythromycin were used . Amoxicillin/clavulanate was associated with a highly significant increase in the risk of necrotizing enterocolitis (RR 4.60, 95% CI 1.98-10.72) . CONCLUSION: The administration of antibiotics after PROM is associated with a delay in delivery and a reduction in maternal and neonatal morbidity . These data support the routine use of antibiotics for women with PROM . Penicillins and erythromycin were associated with similar benefits, but erythromycin was used in larger trials and, thus, the results are more robust . Amoxicillin/clavulanate should be avoided in women at risk of preterm delivery because of the increased risk of neonatal necrotizing enterocolitis . Antibiotic administration after PROM is beneficial for both women and neonates. J Pharm Sci, 2004 Dec, 93(12), 3057 - 65 Two- and three-dimensional QSAR of carrier-mediated transport of beta-lactam antibiotics in Caco-2 cells; Wanchana S et al.; In this study, we investigated whether such a topological descriptor-based approach is suitable for predicting the carrier-mediated transport of 20 beta-lactam antibiotics that are substrates of peptide transporters . To select the molecular descriptors that can effectively predict a targeted property in QSAR analysis, the genetic algorithm-combined partial least squares approach was used . The feasibility of the two-dimensional (2D)-QSAR approach was compared with that of comparative molecular field analysis (CoMFA) . The logarithm of the uptake values of 20 beta-lactam antibiotics in Caco-2 cells obtained from the literature ranged from -1.15 to 1.09 (nmol/cm2/2 h) . When preliminary leave-one-out cross-validated partial least squares analyses implemented in the SYBYL/CoMFA program were conducted, the r2pred was 0.759 and the standard error of prediction (s) was 0.373 . However, the 2D-QSAR approach based on Molconn-Z descriptors gave a better predictability (r2pred = 0.923, s = 0.211), where 14 descriptors were selected and the optimal number of principal components was 4 . Considering that the 2D-topological descriptors are less computationally intensive and practically completely automated, the simple 2D-QSAR model is also of great importance in drug discovery settings . (c) 2004 Wiley-Liss, Inc . and the American Pharmacists Association Shanghai Kou Qiang Yi Xue, 2004 Oct, 13(5), 449 - 51 {A comparison of the effect between Vitapex paste and antibiotic paste in apexification.}; Lu YM et al.; PURPOSE: To study the effects of two root canal filling material in the apexification . METHODS: 172 juvenile permanent teeth,including 62 teeth with pulpitis, 32 teeth with necrotic pulp and 78 teeth with periapical periodontitis, were divided into two groups.The root canal was filled with Vitapex paste and antibiotic paste.Every patient was examined once three months.The treatment lasted 6-30 months.The outcome of treatment was investigated for three years following treatment . RESULTS: The effective rate in the group of Vitapex paste and antibiotic paste group were 86.0% and 91.9% (P>0.05).In periapical periodontitis group,the effective rate of antibiotic paste group was significantly higher than the other (P<0.05) . CONCLUSION: Both Vitapex paste and antibiotics paste were good filling materials in apexification . Antibiotic paste was better than the other in periapical periodontitis group. J Trauma, 2004 Oct, 57(4), 742 - 749 Use of Presumptive Antibiotics following Tube Thoracostomy for Traumatic Hemopneumothorax in the Prevention of Empyema and Pneumonia-A Multi-Center Trial; Maxwell RA et al.; OBJECTIVE:: To determine whether presumptive antibiotics reduce the risk of empyema or pneumonia following tube thoracostomy for traumatic hemopneumothorax . METHODS:: A prospective, randomized, double-blind trial was performed comparing the use of cefazolin for duration of tube thoracostomy placement (Group A) versus 24 hours (Group B) versus placebo (Group C) . RESULTS:: A total of 224 patients received 229 tube thoracostomies . Logistic regression analysis revealed that duration of tube placement and thoracic acute injury score were predictive of empyema (p < 0.05) . Empyema tended to occur more frequently in patients with penetrating injuries (p = 0.09) . chi analysis showed pneumonia occurred significantly more frequently in blunt than penetrating injuries (p < 0.05) . Presumptive antibiotic use did not significantly effect the incidence of empyema or pneumonia, although no empyemas occurred in Group A . CONCLUSIONS:: The incidence of empyema was low and the use of presumptive antibiotics did not appear to reduce the risk of empyema or pneumonia. J Obstet Gynaecol, 1998, 18(4), 315 - 7 Use of steroids, tocolytics and antibiotics in the management of preterm labour in Wales; Savvidou G Edwards N Davies M; Summary The management of preterm labour (PTL) remains contentious . Many regimes are used for the management of this common condition and in utero transfer of pregnant women to another unit is not unusual in British practice . Medical staff in the accepting unit may have little or no experience with one or more drug regimes used in this condition which used in isolation and in combination with others may have disastrous consequences for the mother . We have assessed the variation in practice for the management of preterm labour in all consultant-led obstetric units in Wales using a postal questionnaire . The percentage of units with written guidelines for the management of PTL was 40% . All units used corticosteroids although the regimes used varied . Fourteen of the 15 units used tocolytics . Ritodrine and nifedipine were the most frequently used tocolytics but there was much variation in practice . Only seven (46.7%) units used antibiotics and five of these were randomising women in PTL to the ORACLE study . Postal surveys may not reflect accurately what actually happens in clinical practice . These data demonstrate that there is no common policy for the management of PTL even in a relatively small region such as Wales . We would suggest that the development of a regional policy for the management of preterm labour would be a significant step forward in the management of this controversial, but important cause of neonatal morbidity and mortality. J Obstet Gynaecol, 1997, 17(5), 476 - 8 Use of an experimental model of chlamydial salpingitis in mice for the evaluation of activity of antibiotics and anti-inflammatory drugs on fertility; Verhoest H Sevestre E Bissac And J Orfila P; An experimental animal model has been used to study the separate and combined use of antibiotics and antiinflammatories in the treatment of salpingitis . The addition of an anti-inflammatory did not seem to help preserve fertility. Pol Merkuriusz Lek, 2004 Jun, 16(96), 543 - 6 {Resistance to antibiotics used in Helicobacter pylori infection in children}; Maciorkowska E et al.; In literature and clinical findings, the attention has been turned to the resistance to the antibiotics used in Helicobacter pylori eradication, especially metronidazole and clarithromycin . Drug-resistance was evaluated in 50 children . Primary drug-resistance to the antibiotics used in eradications was determined in this group, and additionally, in 18 children who were subjected twice to unsuccessful eradicative therapy . The highest secondary resistance to metronidazole up to 72.0% was found among conventionally used antibiotics . Primary resistance of H . pylori rods to clariythromycin was also high and equaled 25.0% . However, in our study secondary resistance to macrolids was about 66.0% . In our study combined primary resistance to clarithromycin and metronidazole was about 7.2% . There was not H . pylori rods resistance to amoxicillin and tetracyclines. Perform Improv Advis, 2004 Aug, 8(8), 90 - 1, 85 Guideline urges reduced use of antibiotics after surgery; Antibiotics for the secondary prevention of ischemic heart disease: a meta-analysis of randomized controlled trials; Department of Family Medicine, Medical University of South Carolina, Charleston, SC 29245, USA . wellsbj@musc.edu BACKGROUND: Infections have been suspected in the pathogenesis of ischemic heart disease (IHD) for more than 100 years . Chlamydia pneumoniae has been identified in atherosclerotic specimens, and in some studies antibody titers to C pneumoniae have been related to the risk of myocardial infarction . The numerous clinical trials that have studied the use of antibiotics in the secondary prevention of IHD have had conflicting results . METHODS: This study is a meta-analysis of the published randomized controlled trials on the secondary prevention of IHD with antibiotics . Studies included in the analysis were limited to those studies that used antibiotics effective against C pneumoniae, enrolled patients with known IHD, and examined clinical outcomes related to IHD . Inclusion in the analysis was limited to well-designed randomized controlled trials that met inclusion criteria established by an expert panel . RESULTS: Nine published studies, with a total of 11 015 participants, were identified that met the criteria for this meta-analysis . Four of the studies reported a benefit from antibiotics, whereas 5 found no effect . A funnel plot of the published studies did not suggest the existence of other unpublished data . The combined effect found no benefit from antibiotics in the prevention of cardiovascular events in subjects with known IHD (relative risk, 0.94 {95% confidence interval, 0.86-1.03}) or mortality (relative risk, 0.94 {95% confidence interval, 0.79-1.12}) . CONCLUSION: In patients with known IHD, macrolide antibiotics for C pneumoniae did not result in a statistically significant reduction in recurrent cardiac events or mortality over 3 months to 3 years. Cancer Sci, 2004 Oct, 95(10), 845 - 9 Enhanced antitumor activity of ultrasonic irradiation in the presence of new quinolone antibiotics in vitro; Huang D et al.; To determine if there is any synergistic antitumor effect of ultrasound (US) in the presence of new quinolone (NQ) antibiotics, 0.2 mM solutions of lomefloxacin hydrochloride (LFLX), sparfloxacin (SPFX), ciprofloxacin hydrochloride (CPFX), and gatifloxacin hydrate (GFLX) were tested as sonodynamic agents against sarcoma 180 cells in vitro . After US irradiation at 2 W/cm(2) for 30 and 60 s, the survival rates of tumor cells in the presence of NQ antibiotics were significantly lower than those in their absence (P < 0.001) . In May-Giemsa smears, most of the tumor cells remained intact in the control group . However, in the 0.2 mM SPFX group, the tumor cells were mostly fragmented . The synergistic antitumor effect of SPFX was dose-dependent . Furthermore, when D-mannitol was used with SPFX, the survival rate of tumor cells after irradiation was comparable with that when SPFX alone was applied, but when L-histidine was used concurrently, the survival rate of tumor cells was significantly higher than that when SPFX alone was applied . These findings suggest that NQ antibiotics would exhibit useful antitumor activity under US irradiation, and that generation of singlet oxygen is involved in the process of cell damage. J Hosp Infect, 2004 Nov, 58(3), 187 - 92 Use of antibiotics in hospitals in south-western France; Rogues AM et al.; Data on the use of antibiotics were collected by means of a questionnaire from 49 hospitals in south-western France . Use was expressed as a usage density rate: number of defined daily doses (DDDs) per 1000 patient-days . The average use of antibiotics amounted to 402 DDDs per 1000 patient-days and varied between 60 and 734 . In acute-care wards, the amount of antibiotic use increased with the size of the hospital: 461 DDDs per 1000 patient-days for group A (<100 beds), 510 DDDs per 1000 patient-days for group B (more than 100 and less then 300 beds) and 676 DDDs per 1000 patient-days for group C (>300 beds) . The rate of use differed among different types of hospital areas and varied from 58 for psychiatry departments to more than 1273 DDDs per 1000 patient-days for the infectious diseases departments . Broad-spectrum penicillins were the most frequently prescribed antibiotics . Fluoroquinolone and third-generation cephalosporin use were relatively uniform in the three size categories . This study shows that it is possible for a hospital to benchmark its consumption with other hospitals that are similar in size . In this way, surveillance of antibiotic use can aid hospitals in targeting infection control efforts. Acta Paediatr, 2004 Oct, 93(10), 1386 - 90 Factors of early infancy and recurrent use of antibiotic therapy; Louhi-Pirkanniemi K et al.; AIM: To analyse the role of early infant-related, parent-related, family functioning and social relation factors during the infant's first 3 mo of life and their associations with later recurrent treatments with antibiotics . METHODS: In an unselected population-based study, parents expecting their first child were followed from pregnancy until the infant was 18 mo of age . Informed consent to participate was obtained from 1443 women expecting their first child and their spouses . The parents of 817 children reported the number of preceding antibiotic treatments at two times (when the child was 9 and 18 mo old) . The outcome measure was the number of antibiotic treatments (options: none, 1-5, > or = 6) . The factors associated with later use of antibiotics were collected during the first 3 mo of the infant's life . The variable factors included infant-related, parent-related, family functioning and social relation factors . RESULTS: The final regression analysis showed the potent factors associated with recurrent use of antibiotics: male gender (OR 2.8, 95% CI: 1.6-4.8), frequent physician consultations in early infancy (OR 3.1, 95% CI: 1.8-5.3) and the father's need for outside support (OR 2.2, 95% CI: 1.3-3.8) . CONCLUSIONS: In addition to early infant-related medical factors, family factors may be associated with frequent medical consultations and the decision to administer antibiotics to the infant . In the prevention of antibiotic overuse, social and psychological factors should be considered. Bioorg Med Chem, 2004 Nov 15, 12(22), 5917 - 27 Remarkably different structures and reaction mechanisms of ketoreductases for the opposite stereochemical control in the biosynthesis of BIQ antibiotics; Taguchi T et al.; Two ketoreductases, RED1 and RED2, are involved in the biosynthesis of actinorhodin in Streptomyces coelicolor A3(2) and dihydrogranaticin in S . violaceoruber Tu22, respectively . They are responsible for the stereospecific reductions of the bicyclic intermediate to give (S)- or (R)-DNPA, although there is no similarity between their amino acid sequences . Biotransformation using synthetic analogous substrates revealed that the substrate specificities are quite different . Homology modelling studies and site directed mutagenesis showed remarkable differences in three-dimensional structures and catalytic mechanisms between RED1 and RED2. Berl Munch Tierarztl Wochenschr, 2004 Sep-Oct, 117(9-10), 398 - 403 {Use of aminoglycosides, colistin and beta-lactam antibiotics in animal production (pigs) in Schleswig-Holstein}; Broll S et al.; An evaluation of production orders for medicated feedingstuffs for pigs given in 1998 in Schleswig-Holstein showed aminoglycosides, colistin and beta-lactam antibiotics as regularly used antibiotical ingredients . The presented study analyses the production orders which include these antibiotics more in detail particularly with regard to the prescribed dosages . In part, there were deviations to the rules of good clinical practise for the use of anitbiotics . The applied dosage of spectinomycin and apramycin was often lower than suggested in the literature . The low oral bioavailability of amoxicillin was not considered when using amoxicillin in medicated feedingstuffs. Mil Med, 2004 Sep, 169(9), 728 - 34 Treatment of infected tibial nonunions with debridement, antibiotic beads, and the Ilizarov method; McHale KA et al.; This study of 10 patients presents the early results of a protocol of debridement, antibiotic bead placement, and use of the Ilizarov method with a circular external fixator for treatment of infected nonunions of the tibia in a military population . The nonunions resulted from high-energy fractures in nine cases and an osteotomy in one . The Ilizarov techniques used were transport (five cases), shortening and secondary lengthening (two cases), minimal resection with compression (one case), and resection with bone grafting (two cases) . Flap coverage was required for five patients . There were two recurrences of infection (20%) among patients with the most compromised soft tissue . Only 50% of patients were able to perform limited duties while wearing the external fixator . Only four patients returned to active duty; however, three patients from special operations units were able to return to jump status . Six patients underwent medical retirement because of insufficient function, resulting from decreased ankle or knee range of motion and arthrosis or muscle weakness. Cochrane Database Syst Rev . 2004 Oct 18;(4):CD003367. Antitumour antibiotic containing regimens for metastatic breast cancer; Lord S et al.; BACKGROUND: Antitumour antibiotics are used in the management of metastatic breast cancer . Some of these agents have demonstrated higher tumour response rates than non-antitumour antibiotic regimens, however a survival benefit has not been established in this setting . OBJECTIVES: To identify and review the randomised evidence comparing anti-tumour antibiotic containing chemotherapy regimens with regimens not containing an anti-tumour antibiotic in the management of women with metastatic breast cancer . SEARCH STRATEGY: The specialised register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 2nd May, 2003 using the codes for "advanced breast cancer" and "chemotherapy" . Details of the search strategy and coding applied by the Group to create the register are described in the Group's module on The Cochrane Library . SELECTION CRITERIA: Randomised trials comparing anti-tumour antibiotic containing regimens with regimens not containing anti-tumour antibiotics in women with metastatic breast cancer . DATA COLLECTION AND ANALYSIS: Data were collected from published trials . Studies were assessed for eligibility and quality, and data were extracted by two independent reviewers . Hazard ratios (HRs) were derived from time-to-event outcomes where possible, and a fixed effect model was used for meta-analysis . Response rates were analysed as dichotomous variables . Quality of life and toxicity data were extracted where present . A primary analysis was conducted for all trials and by class of antitumour antibiotic . MAIN RESULTS: Thirty-three trials reporting on 45 treatment comparisons were identified . All trials published results for tumour response and 26 trials published time-to-event data for overall survival . The observed 4084 deaths in 5284 randomised women did not demonstrate a statistically significant difference in survival between regimens that contained antitumour antibiotics and those that did not (HR 0.97, 95% CI 0.91 to 1.03, P = 0.35) and no significant heterogeneity . Antitumour antibiotic regimens were favourably associated with time-to-progression (HR 0.84, 95% CI 0.77 to 0.91) and tumour response rates (odds ratio (OR) 1.34, 95% CI 1.21 to 1.48) although statistically significant heterogeneity was observed for these outcomes . These associations were consistent when the analysis was restricted to the 29 trials that reported on anthracyclines . Patients receiving anthracycline-containing regimens were also more likely to experience toxic events compared to patients receiving non-antitumour antibiotic regimens . No statistically significant difference was observed in any outcome between mitoxantrone-containing and non-antitumour antibiotic-containing regimens . REVIEWERS' CONCLUSIONS: Compared to regimens without antitumour antibiotics, regimens that contained these agents showed a statistically significant advantage for tumour response and time to progression in women with metastatic breast cancer but were not associated with an improvement in overall survival . The favourable effect on tumour response and time to progression observed in anthracycline-containing regimens was also associated with greater toxicity. Metab Eng, 2004 Oct, 6(4), 313 - 25 Metabolic flux analysis for calcium dependent antibiotic (CDA) production in Streptomyces coelicolor; Kim HB et al.; The calcium dependent antibiotic (CDA) is a nonribosomal lipopeptide produced by Streptomyces coelicolor . We constructed a metabolic network of more than 400 reactions for the primary and secondary metabolism of S . coelicolor and used computational metabolic flux balancing to investigate some of the factors affecting growth and production of CDA . Computational results indicated that the CDA production was concomitant with growth . Computational specific growth rates were twice as high as the experimental specific growth rates . Metabolic flux distributions and sensitivity analyses computed for various phases of the batch culture indicated that the specific CDA production rate was affected by nitrogen assimilation, pentose phosphate pathway, shikimate biosynthesis, and oxoglutarate fluxes . Consequently, these metabolic targets were tested using genetic deletions in the model which increased the in silico specific CDA production rate. Annu Rev Microbiol, 2004, 58, 233 - 51 Ribosomal crystallography: initiation, peptide bond formation, and amino acid polymerization are hampered by antibiotics; Yonath A et al.; High-resolution structures of ribosomal complexes revealed that minute amounts of clinically relevant antibiotics hamper protein biosynthesis by limiting ribosomal mobility or perturbing its elaborate architecture, designed for navigating and controlling peptide bond formation and continuous amino acid polymerization . To accomplish this, the ribosome contributes positional rather than chemical catalysis, provides remote interactions governing accurate substrate alignment within the flexible peptidyl-transferase center (PTC) pocket, and ensures nascent-protein chirality through spatial limitations . Peptide bond formation is concurrent with aminoacylated-tRNA 3' end translocation and is performed by a rotatory motion around the axis of a sizable ribosomal symmetry-related region, which is located around the PTC in all known crystal structures . Guided by ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in stereochemistry that is optimal for peptide bond formation and for nascent protein entrance into the exit tunnel, the main target of antibiotics targeting ribosomes . By connecting the PTC, the decoding center, and the tRNA entrance and exit regions, the symmetry-related region can transfer intraribosomal signals, guaranteeing smooth processivity of amino acid polymerization. Ambix, 2004 Jul, 51(2), 167 - 85 Networks of innovation or networks of opportunity? The making of the Spanish antibiotics industry; Puig N; The pharmaceutical industry is a typically research-intensive, first world-industry . This article seeks to explain why it has been so difficult for late industrialised nations to reproduce the networks of innovation on which the design and manufacturing of new drugs has historically based, and why alternative concepts are needed in order to understand the dynamics of science-based industries in emerging countries . The article analyses the development of the Spanish antibiotics industry, build after the World War II under the strong influence of the new international order and Spain's political framework, academic traditions and business groups . Focusing on the long-term relationships established between two Spanish companies (Antibioticos SA and Compania Espanola de Penicilina y Antibioticos, CEPA), their American technological partners (Schenley and Merck), and their social and scientific environment, the article identifies networks of opportunity as the key institutional arrangement of this new industry in Spain . Opportunity (as opposed to innovation) networks are thus proposed to conceptualise the development of technologically complex industries in the European periphery. AIDS Treat News . 2004 Aug 27;(404):7. Empty antibiotic pipeline critically endangers public: IDSA report; James JS; A huge decrease in the number of fundamentally new antibiotics--driven by commercial not scientific problems--seriously threatens public health in the near future, as bacteria develop resistance to the existing drugs, and previously treatable infections will often be fatal. J Biomed Mater Res B Appl Biomater, 2005 Jan 15, 72(1), 191 - 7 Poly (acrylic acid) chitosan interpolymer complexes for stomach controlled antibiotic delivery; de la Torre PM et al.; The aim of this study was to develop a stomach-specific drug delivery system to increase the efficacy of amoxicillin against Helicobacter pylori . Polyacrylic acid (PAA), chitosan (CS), and amoxicillin (A) were employed to obtain polyionic complexes . The design of the hydrogel delivery system was based on the swellable approach; with a floating feature to prolong the Gastric Residence Time (GRT) . The polyionic complex (PAA:CS:A 2.5:5:2) showed a sustained drug release profile in enzyme-free simulated gastric fluid (SGF) and pH 4.0 . A pH independent swelling-eroding pattern with adequate maximum swelling ratios of 17.76 and 13.42 was obtained at in SGF and pH 4.0, respectively, with similar eroding profiles in both pH media . This network carrier provides an amoxicillin protective effect towards the hydrolytic degradation in SGF . The in vivo study was performed on healthy volunteers, using the {13C} octanoic acid breath test . The proposed hydrogel showed a prolonged GRT of up to 3 h . The preliminary results from this study suggest that amoxicillin polyionic complexes have potential for improving local antibiotic therapy against H . pylori . Pediatr Surg Int . 2004 Oct 6; {Epub ahead of print} Minimum postoperative antibiotic duration in advanced appendicitis in children: a review; Snelling CM et al.; The suitable duration of antibiotic use following appendectomy for advanced appendicitis in children is still debated . A systematic review was performed, including published experimental and observational data of antibiotic use in children who had undergone appendectomy for advanced appendicitis . Data were extracted and analyzed according to predefined criteria . Twenty-eight studies were selected that included 2,284 patients . There was no consistency among the protocols regarding length of antibiotic use, discharge criteria, or use of home antibiotics following discharge . Limiting duration of antibiotic use to3 days did not appear to be associated with higher rates of intraabdominal abscess or wound infection . In the absence of higher-level evidence, shortening of antibiotic regimens following surgery for pediatric complicated appendicitis appears to be safe. Childs Nerv Syst . 2004 Oct 12; {Epub ahead of print} Initial experience with antibiotic-impregnated silicone catheters for shunting of cerebrospinal fluid in children; Aryan HE et al.; INTRODUCTION . Infection is a major complication of cerebrospinal fluid (CSF) shunting procedures . Recently, rifampin-impregnated and clindamycin-impregnated silicone catheters have been developed in an attempt to prevent and/or reduce the incidence of shunt infections . In vitro and in vivo animal studies have shown their efficacy in reducing bacterial colonization of catheters . However, these shunts are yet to be evaluated in clinical trials and their safety and efficacy in preventing shunt infections is unknown . METHODS . Between April 2002 and April 2003, 31 children (age range 6 months to 17 years, mean 4.5 years) underwent implantation of an antibiotic-impregnated silicone catheter for CSF diversion . All surgeries were performed by a single neurosurgeon (HSM) at a single medical center . The Codman Hakim Bactiseal silicone catheter was used in all children . Thirty-two catheters were implanted in 31 children . All children have been followed since surgery (for an average of 19 months) . For comparison, the previous 46 standard implanted shunts over a similar period of time were reviewed (average follow-up 31 months) . RESULTS . Of the 32 implanted catheters, 11 involved placement of a new complete shunt system, 8 were distal revisions, and 13 were proximal/ventricular revisions . There were fewer early and late complications than in the standard shunt group (12.5 and 18.8% vs . 23.9 and 34.8%) . There was no local reaction from implantation of the catheters . One child contaminated his distal catheter by disrupting his abdominal incision . None of the other patients have developed any evidence of shunt infection to date . CONCLUSION . Rifampin-impregnated and clindamycin-impregnated silicone catheters appear to be safe and well tolerated in children . Preliminary results suggest a low incidence of shunt infection . Longer follow-up and a larger number of patients are needed to more accurately assess the efficacy of these catheters compared with traditional silicone catheters. Kansenshogaku Zasshi, 2004 Aug, 78(8), 717 - 21 {Epidemiological investigation of beta-lactam antibiotic induced vancomycin-resistant MRSA from clinical isolated MRSA--comparison of detection rate of BIVR with or without CZX}; Hososaka Y et al.; Recently, beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR) has been reported increasingly in Japan . Between 1998 and 2002, we tried to detect BIVR from 500 strains of MRSA in a cancer hospital . And the difference of the detection rate under condition of pre-culture with or without ceftizoxime was compared . The detection rate of BIVR under condition of pre-culture with 1.0 mg/L of ceftizoxime was 20.4% (102/500), and without ceftizoxime was 9% (45/500) . That of preculture with 1.0 mg/L of ceftizoxime was higher than those without ceftizoxime with the significant difference . (p < 0.001; McNemar-t examination) . In comparing each department, the detection rate of BIVR from Chemotherapy, Head & Neck, and Urology department was 33.3%, 27.0%, and 20.0%, respectively . These results mean that addition of beta-lactam as ceftizoxime in pre-culture induces the ability of resistance to vancomycin for MRSA having a capacity as BIVR. Biotechnol Bioeng, 2004 Dec 5, 88(5), 652 - 63 Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp . ATCC 39727; Gunnarsson N et al.; The actinomycete Nonomuraea sp . ATCC 39727, producer of the glycopeptide A40926 that is used as precursor for the novel antibiotic dalbavancin, has an unusual carbon metabolism . Glucose is primarily metabolized via the Entner-Doudoroff (ED) pathway, although the energetically more favorable Embden-Meyerhof-Parnas (EMP) pathway is present in this organism . Moreover, Nonomuraea utilizes a PPi-dependent phosphofructokinase, an enzyme that has been connected with anaerobic metabolism in eukaryotes and higher plants, but recently has been recognized in several actinomycetes . In order to study its primary carbon metabolism in further detail, Nonomuraea was cultivated with {1-13C} glucose as the only carbon source and the 13C-labeling patterns of proteinogenic amino acids were determined by GC-MS analysis . Through this method, the fluxes in the central carbon metabolism during balanced growth were estimated . Moreover, a shift in the label incorporation pattern was observed in connection with phosphate limitation and increased antibiotic productivity in Nonomuraea . The shift indicated an increased flux through the EMP pathway at the expense of the flux through the ED pathway, a suggestion that was supported by alterations in intracellular metabolite levels during phosphate limitation . In contrast, expression levels of genes encoding enzymes in the ED and EMP pathways were not affected by phosphate limitation. J Vasc Surg, 2004 Oct, 40(4), 826 - 9 Aortobifemoral graft infection with Mycobacterium tuberculosis: treatment with abscess drainage, debridement, and long-term administration of antibiotic agents; Raffetto JD et al.; Aortic graft infection with Mycobacterium tuberculosis is rare . We report a patient with a Dacron aortobifemoral prosthetic graft infection secondary to tuberculosis . The infection was successfully treated with surgical drainage without removal of the graft, and long-term antimycobacterial medications . A review of the literature contains only 1 other report of tuberculosis graft infection and treatment . We discuss a rare form of aortic graft infection from M tuberculosis and its treatment. Shokuhin Eiseigaku Zasshi, 2004 Jun, 45(3), 161 - 4 {Simultaneous determination of residual fourteen kinds of beta-lactam and macrolide antibiotics in bovine muscles by high-performance liquid chromatography with a diode array detector}; Nagata T et al.; Residues of 14 kinds of beta-lactam and macrolide antibiotics in bovine muscles were extracted with acetonitrile and the extract was partitioned with n-hexane to remove fat . High-performance liquid chromatography was carried out on a TSK-gel ODS-80TM column using gradient elution with acetonitrile-0.05% trifluoroacetic acid and the drugs were quantitated by diode array detection . The recoveries of the drugs from bovine muscles spiked at 0.1 ppm were over 63% and each quantitation limit was 0.04 ppm. Magn Reson Chem, 2005 Jan, 43(1), 16 - 20 Determination of the three-dimensional, solution-phase structure of the macrolide antibiotic oxolide in CD(2)Cl(2) and D(2)O from NMR constraints; Steinmetz WE et al.; The three-dimensional structure of the antibiotic oxolide, (9S,11S)-11-amino-9-deoxo-11,12-deoxy-9,12-epoxyerythromycin, was determined in CD(2)Cl(2) through constrained molecular mechanics with constraints derived from proton NMR . The calculations yielded a well-defined global minimum . Data acquired for oxolide in D(2)O, although not as complete, indicate that the antibiotic adopts the same conformation in water . Copyright (c) 2004 John Wiley & Sons, Ltd. J Cyst Fibros, 2002 Dec, 1(Suppl 2), 209 - 14 Inhaled antibiotic therapy in evidence: what delivery device? Dennis JH, Pieron CA. This paper evaluates the suitability of various compressors available in Europe to generate and deliver tobramycin nebulizer solution to cystic fibrosis patients from the PARI LC PLUS jet nebulizer . This evaluation has been undertaken (i) by establishing an in vitro equivalence to the DeVilbiss PulmoAide compressor (operating at 4.6 l/min) proven effective in US clinical trials, and (ii) by determining equivalent in vitro performance of the LC PLUS nebulizer driven by alternative airflows . Equivalent performance is judged as having both an aerosol output and aerosol size within +/-10% of that obtained with the LC PLUS/PulmoAide combination . The two different in vitro methodologies applied to this investigation were based on the British Standard and a European Standard to assess nebulizer output . The results demonstrate that a wide range of compressed airflow rates generate aerosol output from the PARI LC PLUS equivalent to that obtained from the PulmoAide compressor . This range of airflows encompasses many compressors commonly available in Europe. Allergy, 2004 Nov, 59(11), 1153 - 60 Diagnosis of nonimmediate reactions to beta-lactam antibiotics; Romano A et al.; Nonimmediate manifestations (i.e . occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common during beta-lactam treatment . The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood . However, clinical and immunohistological studies, as well as analysis of drug-specific T-cell clones obtained from the circulating blood and the skin, suggest that a type-IV (cell-mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis . In the diagnostic work-up, the patient's history is fundamental; patch testing is useful, together with delayed-reading intradermal testing . The latter appears to be somewhat more sensitive than patch testing, but also less specific . In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents . With regard to in vitro tests, the lymphocyte transformation test may contribute to the identification of the responsible drug . Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions to beta-lactams . Langmuir, 2004 Oct 12, 20(21), 9270 - 5 Aminoglycoside antibiotics aggregate to form starch-like fibers on negatively charged surfaces and on phage lambda-DNA; Kopaczynska M et al.; The water-soluble (> 200 mg/mL) antibiotics tobramycin, kanamycin, and neomycin spontaneously produce rigid fibers on negatively charged surfaces (mica, graphite, DNA) . Atomic force microscopy showed single strands of tobramycin on mica at pH 7 with a length of several hundred nanometers and a diameter of 0.5 nm and double helices with a diameter of 1.0 nm and a helical pitch of 7 nm . At pH 13 (NaOH) up to 15 microm long, rigid fibers with a uniform height of 2.4 nm and an apparent helical pitch of 30 nm were formed along the sodium silicate channels on the surface of mica . Kanamycin and neomycin behaved similarly . Fibers of similar length and width, but without secondary structure, were obtained from aqueous solutions at pH 7 on amorphous, hydrophilized carbon and characterized by transmission electron microscopy . Overstretched phage lambda-DNA strands with a height of 1.0 nm on mica did not interact with tobramycin coils at pH 7 . After treatment with EDTA, however, the height of the magnesium-free lambda-DNA strands grew from 1.0 to 3.8 nm after treatment with tobramycin, which suggests a wrapping by the supramolecular fibers . Such fibers may interact with F-actin fibers in biological cells, which would explain the known aggressiveness of aminoglycosides toward bacterial cell membranes and their ototoxicity . Mol Biotechnol, 2004 Sep, 28(1), 47 - 62 Resistance to macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics; Roberts MC; Macrolides have enjoyed a resurgence as new derivatives and related compounds have come to market . These newer compounds have become important in the treatment of community-acquired pneumoniae and nontuberculosis-Mycobacterium diseases . In this review, the bacterial mechanisms of resistance to the macrolide, lincosamide, streptogramin, ketolide, and oxazolidinone antibiotics, the distribution of the various acquired genes that confer resistance, as well as mutations that have been identified in clinical and laboratory strains are examined. J Biol Chem, 2004 Dec 10, 279(50), 52075 - 81 Epub 2004 Dec 10. Functional characterization of Escherichia coli DNA adenine methyltransferase, a novel target for antibiotics; Mashhoon N et al.; We have characterized Escherichia coli DNA adenine methyltransferase, a critical regulator of bacterial virulence . Steady-state kinetics, product inhibition, and isotope exchange studies are consistent with a kinetic mechanism in which the cofactor S-adenosylmethionine binds first, followed by sequence-specific DNA binding and catalysis . The enzyme has a fast methyl transfer step followed by slower product release steps, and we directly demonstrate the competence of the enzyme cofactor complex . Methylation of adjacent GATC sites is distributive with DNA derived from a genetic element that controls the transcription of the adjacent genes . This indicates that the first methylation event is followed by enzyme release . The affinity of the enzyme for both DNA and S-adenosylmethionine was determined . Our studies provide a basis for further structural and functional analysis of this important enzyme and for the identification of inhibitors for potential therapeutic applications. Bull Exp Biol Med, 2004 May, 137(5), 483 - 4 Detection of mutant Mycoplasma hominis strains resistant to 16-membered macrolide antibiotic josamycin in clinical samples; Karamova AE et al.; The incidence of point mutations responsible for josamycin resistance was studied by PCR in 48 strains of M . hominis isolated from patients with bacterial vaginosis . Mutant M . hominis strains were detected in 48% cases. J Public Health (Oxf), 2004 Sep, 26(3), 268 - 74 Why has antibiotic prescribing for respiratory illness declined in primary care? A longitudinal study using the General Practice Research Database; Ashworth M et al.; BACKGROUND: Antibiotic prescribing by general practitioners (GPs) increased in the 1980s and peaked in 1995 . Prescribing volumes subsequently fell by over a quarter between 1995 and 2000, mostly accounted for by reduced antibiotic prescribing for acute respiratory illnesses . We aimed to investigate changes in consultation rates and the proportion of consultations with antibiotics prescribed for different types of respiratory tract infections . METHODS: Data were derived from 108 UK general practices, covering a mean of 642,685 patients, reporting data to the General Practice Research Database (GPRD) continuously between 1994 and 2000 . Outcome measures: annual age- and sex-standardized consultation rates for 11 different acute respiratory infections per 1000 registered patients and proportions of these consultations resulting in an antibiotic prescription . RESULTS: The standardized consultation rate for 'any respiratory infection' declined by 35 per cent from 422 to 273 per 1000 registered patients, per year . The largest relative reductions in consultation rates were observed for 'common cold' (50 per cent), 'laryngitis' (43 per cent) and 'sore throat' (43 per cent) . The standardized proportion of consultations that resulted in an antibiotic prescription for 'any respiratory infection' declined from 79 per cent in 1994 to 67 per cent in 2000 . The largest relative reductions in antibiotic prescribing rates occurred in patients recorded as suffering from 'influenza' (52 per cent), 'upper respiratory tract infections' (33 per cent) and 'laryngitis' (30 per cent) . Overall, antibiotic prescriptions for all acute respiratory infections declined by 45 per cent . CONCLUSION: The reduction in antibiotic prescribing in common respiratory infections between 1994 and 2000 has occurred partly because GPs are prescribing antibiotics less frequently when patients consult but mainly because there are fewer consultations with these conditions . Further work should aim to understand the reasons for the decline in consultations for respiratory infections and whether further reductions in antibiotic prescribing are feasible. Toxicol Appl Pharmacol, 2004 Oct 1, 200(1), 16 - 26 Quantitative gene expression analysis in a nonhuman primate model of antibiotic-induced nephrotoxicity; Davis JW 2nd et al.; Gene expression patterns using microarrays have been described for rodent models of nephrotoxicity . To determine if significant gene expression changes previously identified have application across multiple species, we studied quantitative gene expression changes in the kidneys of female cynomolgus monkeys after exposure to two nephrotoxicants . Animals were dosed with the aminoglycoside gentamicin (10 mg/kg), the experimental oligosaccharide antibiotic everninomicin (30 or 60 mg/kg), or a combination of gentamicin (10 mg/kg) and everninomicin (30 mg/kg) for 7 days . Monkeys receiving these drugs in combination developed renal lesions as early as Day 1 . By Day 7, monkeys dosed with 60 mg/kg everninomicin alone also developed renal lesions, while the group exposed to both compounds had more extensive renal damage . The modulation of several genes previously reported to be associated with nephrotoxicity in rodent models was confirmed using quantitative real-time PCR . Among these, waf-1, matrix metalloproteinase-9, and vimentin exhibited changes consistent with the definition of a genomic indicator of toxicity . In addition, we identified three early gene biomarkers that may be predictive of drug-induced nephrotoxicity: clusterin, osteopontin, and hepatitis A virus cellular receptor-1 . Logistic regression demonstrated a high degree of correlation between changes in gene expression and the probability of the development of histopathologic lesions . These results are the first confirming rodent gene expression changes associated with nephrotoxicity in a nonhuman primate model and provide preliminary evidence for identifying early gene expression changes predicting the onset of drug-induced renal tubular damage in cynomolgus monkeys. Dig Dis Sci, 2004 Aug, 49(7-8), 1280 - 6 High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn's disease: a pilot study; Mow WS et al.; In Crohn's disease, antibiotics are used with variable efficacy, suggesting that some patients are more likely to respond . The aim of this study was to determine whether Crohn's patients with predominant serum antibody reactivity toward bacterial antigens OmpC and/or I2 were more likely to achieve remission with antibiotics . Patients with ileal or ileal with right-sided colonic Crohn's disease were studied in a double-blind trial of budesonide alone or budesonide plus metronidazole and ciprofloxacin . In the budesonide plus metronidazole and ciprofloxacin group, patients with OmpC/I2 predominant profiles had the highest remission rate, whereas the group with no antibody predominant profiles had the lowest rate . In the budesonide group, patients with the OmpC/I2 predominant profile had the lowest remission rate, and the no-antibody group rate was higher . Although not statistically significant, these results support further testing to determine whether predominant serum reactivity to certain bacterial antigens may be a marker for efficacious use of antibiotics. Pharmacoepidemiol Drug Saf . 2004 Aug 25; {Epub ahead of print} Antibiotic utilisation in community practices: guideline concurrence and prescription necessity; Jelinski S et al.; PURPOSE: To evaluate the indications, concurrence with prescribing guidelines and potential necessity for antibiotic (AB) prescriptions written in community practice . METHODS: We reviewed the charts of all patients with infection-related illnesses seen by family physicians during two random days of regular practice between 1 Oct 1997 and 30 Jan 1998 . Guideline concurrence of AB prescribing was assessed using regional AB prescribing guidelines . Likelihood of AB indication for respiratory tract infections was assessed using published clinical practice guidelines for determination of likely viral versus bacterial etiology . RESULTS: Of 4218 visits captured, 949 (22%) were for newly acquired infections . Sixty four percent (n = 604) of consultations for newly acquired infections resulted in an AB prescription . Based on the doctors' diagnoses, 61% of AB prescriptions were concurrent with prescribing guidelines, 10% were for the wrong drug, 20% were not indicated and in 10% of cases a lower line AB was available . For respiratory tract infections, 12% of these infections were likely bacterial, whereas the physicians determined that 56% were bacterial . CONCLUSIONS: A large proportion of ABs administered in community practices were not in concurrence with community AB prescribing guidelines . Improvements can be made in AB choice and in decisions about likely viral etiology for respiratory tract infections . J Immunol, 2004 Oct 1, 173(7), 4652 - 60 The antibiotic polymyxin B modulates P2X7 receptor function; Ferrari D et al.; The natural peptide polymyxin B (PMB) is a well-known and potent antibiotic that binds and neutralizes bacterial endotoxin (LPS), thus preventing its noxious effects among LPS-mediated endotoxin shock in animal models . We have investigated the effect of PMB on responses mediated by the P2X(7)R in HEK293 and K562 cells transfected with P2X(7) cDNA and in mouse and human macrophages . In addition, in view of the potential exploitation of P2X(7)-directed agonists in antitumor therapy, we also investigated the effect of PMB in B lymphocytes from patients affected by chronic lymphocytic leukemia . PMB, at an optimal concentration dependent on the given cell type, greatly potentiated the effect of nucleotide-mediated P2X(7) stimulation . In particular, ATP-mediated Ca(2+) influx, plasma membrane permeabilization, and cytotoxicity were enhanced to an extent that, in the presence of PMB, cells were killed by otherwise ineffective nucleotide concentrations . The synergistic effect due to the combined application of ATP and PMB was prevented by incubation with the irreversible P2X blocker oxidized ATP (oATP), but not with the reversible antagonist 1-(N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl)-4-phenilpiperazine (KN-62) . Cells lacking P2X(7) were fully insensitive to the combined stimulation with PMB and ATP . Furthermore, PMB at the concentrations used had no untoward effects on cell viability . These results point to PMB as a useful tool for the modulation of P2X(7)R function and suggest that care should be used in the evaluation of ATP-stimulated immune cell responses in the presence of PMB as they may not solely be affected by removal of contaminating LPS. Arch Otolaryngol Head Neck Surg, 2004 Sep, 130(9), 1084 - 7 Pulmonary complications following major head and neck surgery with tracheostomy: a prospective, randomized, controlled trial of prophylactic antibiotics; Ong SK et al.; OBJECTIVE: To test the hypothesis that extended postoperative antibiotic cover would reduce the incidence of pulmonary complications in patients undergoing major head and neck surgery with tracheostomy . DESIGN: A prospective, randomized, controlled trial was carried out to determine the efficacy of an extended course (5 days) of intravenous amoxicillin-clavulanic acid in reducing the rate of atelectasis and pulmonary infections postoperatively . Other possible risk factors that might predispose to pulmonary complications were also evaluated . SETTING: Tertiary referral center for head and neck surgery . PATIENTS: Consecutive patients younger than 80 years with planned surgery for carcinoma of the oral cavity, pharynx, or larynx were enrolled . Patients with diabetes, those who had received antibiotics within 1 week before surgery, and those with preexisting pulmonary disease were excluded . INTERVENTION: Patients were randomly assigned no antibiotics or a 5-day course of intravenous amoxicillin-clavulanic acid postoperatively . MAIN OUTCOME MEASURES: The development of pulmonary complications (pulmonary infection or atelectasis) . RESULTS: Eighty-six patients were enrolled; 73 patients met the criteria for analysis . Thirty-four (47%) developed pulmonary complications; 29 (40%) had a pulmonary infection . An extended course of antibiotics did not reduce the rate of pulmonary infections (P =.57) . Positive risk factors for a pulmonary infection were presence of preoperative obstructive lung function and postoperative atelectasis . CONCLUSIONS: An extended course of antibiotics did not prevent the development of postoperative pulmonary infections in patients undergoing major head and neck surgery with tracheostomy . Poor pulmonary function and postoperative atelectasis emerged as significant risk factors for pulmonary infection. J Chromatogr A, 2004 Aug 6, 1045(1-2), 111 - 7 Fast and robust simultaneous determination of three veterinary antibiotics in groundwater and surface water using a tandem solid-phase extraction with high-performance liquid chromatography-UV detection; Blackwell PA et al.; A simple and robust analytical method is presented in which the three veterinary antibiotics oxytetracycline (OTC), sulfachloropyridazine (SCP) and tylosin (TYL) were simultaneously determined in surface water and groundwater . The three compounds were simultaneously extracted from the water samples using a mixture of methanol, EDTA and McIlvaine buffer (citric acid and sodium orthophosphate) and then cleaned-up and pre-concentrated by solid-phase extraction using sacrificial Isolute strong anion-exchange cartridges, to remove interfering organic material, and Waters Oasis hydrophilic-liphophilic balance polymer cartridges, to retain the compounds, in tandem . Analysis was performed using liquid chromatography with ultraviolet detection . Recoveries for river water samples spiked at 10 and 1 microgl(-1) were respectively 99.6+/-4.6 and 99.4+/-8.4% for OTC; 99.9+/-2.2 and 105.0+/-5.7% for SCP; and 94.9+/-2.4 and 71.6+/-8.2% for TYL . Overall limits of detection based on pre-concentrating 400 ml of sample were 0.35 microgl(-1) for OTC and TYL and 0.25 microgl(-1) for SCP. J Antimicrob Chemother, 2004 Nov, 54(5), 904 - 8 Epub 2004 Sep 16. Post-antibiotic effect induced by an antibiotic combination: influence of mode, sequence and interval of exposure; Li RC et al.; OBJECTIVES: The effects of mode, sequence and interval of antibiotic exposure on the post-antibiotic effect (PAE) induced by rifampicin and tobramycin were studied using Escherichia coli ATCC 25922 as the test organism . METHODS: In triplicate, baseline PAEs were evaluated by exposing E . coli to rifampicin and tobramycin individually and simultaneously for 1 h . PAEs were further assessed in a second study, with the organism exposed first to rifampicin for 1 h, followed by a second 1 h tobramycin exposure, commencing at the beginning, middle and end of the PAE phase induced by rifampicin . The third study was similar to the above, but with the sequence of the two antibiotics reversed, i.e . tobramycin then rifampicin . RESULTS: The PAE produced by simultaneous exposure of the combination showed an apparent additive interaction (PAE: 5.0+/-0.3 h) when compared with the PAE of individual antibiotics (rifampicin alone: 3.0+/-0.1 h; tobramycin alone: 1.5+/-0.1 h) . However, an antagonistic interaction was observed in the second study, with a more pronounced degree of antagonism at the beginning, dissipating towards the end of the previous rifampicin PAE (PAE at the beginning: 2.6+/-0.3 h; the middle: 1.5+/-0.2 h; and at the end: 1.7+/-0.3 h) . By subtracting the residual contribution from the first rifampicin exposure, the net average PAEs attributed to the second tobramycin exposure actually increased, from -0.4 to 1.7 h from the beginning to the end of the rifampicin PAE . For the third study, an additive interaction was again observed when the organism was exposed to tobramycin first (PAE at the beginning: 4.7+/-0.4 h; the middle: 3.7+/-0.7 h; and at the end: 3.1+/-0.4 h) . The timing of the second rifampicin exposure had no impact to the interaction; after correction, the net mean PAEs attributed to the second rifampicin exposure were maintained at 3.2, 3.2 and 3.1 h . CONCLUSIONS: The present data suggest that the expression of interaction type on PAE by an antibiotic combination was dependent on the mode, sequence and interval of exposure . The impact of these variables should not be overlooked when clinical dosing regimens are optimized. Chembiochem, 2004 Sep 6, 5(9), 1228 - 36 Disaccharide mimetics of the aminoglycoside antibiotic neamine; Venot A et al.; A highly convergent approach has been employed for the facile synthesis of a library of 24 disaccharides that are alpha(1-3), beta(1-3), alpha(1-4), or beta(1-4) linked and contain 2-4 amino groups . Fourier-transformation ion cyclotron resonance mass spectrometry (FT-ICR MS) has been used to determine dissociation constant (Kd) values for the binding of the disaccharides to a prototypical fragment of 16S ribosomal RNA . Several derivatives bound with affinities similar to that of neamine . Structure-activity relationships have revealed the substitution pattern that is important for high-affinity binding . The compounds described here are unique lead compounds for the design of novel aminoglycoside antibiotics. Chembiochem, 2004 Sep 6, 5(9), 1181 - 7 Genetic organization of the biosynthetic gene cluster for the antitumor angucycline oviedomycin in Streptomyces antibioticus ATCC 11891; Lombo F et al.; The oviedomycin biosynthetic gene cluster from Streptomyces antibioticus ATCC 11891 has been sequenced and characterized . It contains all the necessary genes for oviedomycin biosynthesis, together with several genes for the generation of malonyl-CoA extender units . Production of this unusual angucyclinone in its natural host occurs only in solid cultures in parallel with aerial mycelium and spore formation . A mutant that did not produce oviedomycin was generated by disruption of the beta-ketoacyl synthase gene ovmK . No other physiological process in the mutant appears to be affected; this rules out a direct relationship between oviedomycin production and cell differentiation in S . antibioticus. Fam Pract, 2004 Oct, 21(5), 500 - 6 Acute cough: a qualitative analysis of how GPs manage the consultation when patients explicitly or implicitly expect antibiotic prescriptions; Altiner A et al.; OBJECTIVE: The aim of this study was to analyse how GPs manage the consultation for acute cough when patients explicitly or implicitly expect antibiotic prescriptions . METHODS: A qualitative analysis of audio-taped consultations was carried out . The participants were eight GPs from eight general practices in Northrhine, Germany and their 42 patients with acute cough over a 2 week period . Three researchers analysed the consultations independently, finally agreed by discussion . RESULTS: Implicit expectations for antibiotics were found frequently, but in none of the 42 consultations was the patient asked directly what she or he expected in terms of therapy . The topic of expectations and demands itself normally was not discussed at all, not even in a non-direct manner . In some consultations, the possibility of an antibiotic prescription was ruled out by the GP from the beginning . In some consultations, even a 'pseudo-consent' was found, avoiding any explicit clarification . CONCLUSION: GPs seem to overestimate the actual pressure to prescribe antibiotics for acute cough . The (over) prescription of antibiotics might not be a question of knowledge but a lack of patient centredness. Fam Pract, 2004 Oct, 21(5), 492 - 9 Perceptions of patient expectation for an antibiotic: a comparison of walk-in centre nurses and GPs; Weiss MC et al.; BACKGROUND: Patient expectation for a prescription is a recognized influence on GPs' prescribing, particularly in relation to the prescribing of antibiotics . Nurses are now able to supply antibiotics under a Patient Group Direction (PGD) in NHS walk-in centres and may experience similar pressures in this new role . OBJECTIVES: Our aim was to compare walk-in centre nurses' and GPs' perceptions of the influence of patient expectation on their supply of an antibiotic to patients with an acute respiratory tract infection presenting with a sore throat or cough . METHODS: Between June and December 2001, all patients presenting with a sore throat or cough at six walk-in centres and six nearby general practices were eligible to participate in the study . After the health professional-patient consultation, the health professional and the patient each completed a questionnaire . RESULTS: There were 472 health professional (181 GPs and 291 walk-in centres) and 160 (34%, 160 out of 472) patient questionnaires returned . GPs were more likely to report that the patient expected an antibiotic than nurses (72% of 181 versus 13% of 291, P < 0.001) . GPs were also less likely to report that an antibiotic was indicated than nurses (88% of 136 versus 97% of 194, P < 0.001) . There was a trend for doctors to prescribe more frequently than nurses, in 74% of 180 patients versus 66% of 291 patients (P = 0.06) . GPs were likely to report that the patient expected an antibiotic when the patient reported wanting a prescription (60% of 68, P = 0.05) and to report that the patient expected an antibiotic if the patient thought an antibiotic would be beneficial (62% of 68, P = 0.001) . There was a much weaker relationship between nurse perceptions of patient expectation for an antibiotic and, either patient desire for a prescription or the patient's affirmative belief that an antibiotic would be beneficial . CONCLUSIONS: Nurses may be compensating for a lack of security in their new role as antibiotic suppliers by not acknowledging the influence of patient expectation on their decision making . The acknowledgement of the influence of patient expectation might be beneficial to nurses' development as suppliers of medicines by giving them greater understanding of the consultation process and in the need to discuss patient expectations explicitly in the consultation. Z Kardiol, 2004 Sep, 93(9), 671 - 8 Antibody levels against Chlamydia pneumoniae and outcome of roxithromycin therapy in patients with acute myocardial infarction . Results from a sub-study of the randomised Antibiotic Therapy in Acute Myocardial Infarction (ANTIBIO) trial; Burkhardt U et al.; BACKGROUND: Results of studies concerning prevention of cardiovascular disease by treatment with macrolide antibiotics targeting C . pneumoniae infection are still controversial . This study describes the results of different tests for infection with C . pneumoniae as well as the effect of treatment with roxithromycin in patients with acute myocardial infarction (AMI) in relation to their serostatus against C . pneumoniae . METHODS: We analysed blood of 160 patients who came from the ANTIBIOtic therapy after an AMI ( ANTIBIO-) study, a prospective, randomised, placebo-controlled, double-blind study to investigate the effect of roxithromycin 300 mg/OD for 6 weeks in patients with an AMI . Anti- Chlamydia IgG-, IgA-, and IgM-antibodies of these patients were analysed by means of different test systems . RESULTS: There was a good correlation between the two IgG and IgA methods (r = 0.900, p < 0.001 and r = 0.878, p < 0.001, respectively), but marked differences in the prevalence of positive tests . This resulted in only moderate concordance values, as expressed by the Kappa coefficients, for IgG kappa = 0.611 (95% CI = 0.498-0.724, p < 0.001) and for IgA kappa = 0.431 (95% CI: 0.322-0.540, p < 0.001) . No significant association between positive C . pneumonia titers and the combined clinical endpoint during the 12 month follow-up could be found . In all test systems used, patients with positive anti- C . pneumoniae titers did not benefit from roxithromycin therapy (p = ns) . CONCLUSION: Depending on the test system used, there are large differences in the prevalence of anti- C . pneumoniae seropositive patients . Clinical events during the 12 month follow-up after AMI did not depend on serostatus against C . pneumoniae and treatment with roxithromycin did not influence these events, independently of the serostatus against C . pneumoniae . However, the power of this subgroup analysis was low to detect small but significant differences. Anal Bioanal Chem, 2004 Sep, 380(1), 123 - 8 Epub 2004 Jul 28. Stability of fluoroquinolone antibiotics in river water samples and in octadecyl silica solid-phase extraction cartridges; Turiel E et al.; Intensive use of antibiotics in human and veterinarian medicine and in industrial farming (food additives) has resulted in the transport of important quantities of the active ingredients to environmental waters . Environmental analysis usually requires sample storage for certain periods of time and, consequently, it is of great importance to know the stability of antibiotics in these kinds of sample . Thus, in this work the stability in river water of oxolinic acid (Oxo) and ciprofloxacin (Cip), taken as representatives of fluoroquinolone and quinolone antibiotics respectively, has been evaluated . The stability of these compounds in river water has been studied both in containers and on C(18) solid-phase extraction cartridges (SPE) under different storage conditions (time, light, and temperature) . Data analysis revealed that Cip and Oxo have different degradation profiles with different degradation kinetics in river water . It was also concluded that these antibiotics are stable both in the containers and on SPE cartridges for at least 2 weeks at ambient temperature, and stability can be increased substantially if samples are stored at low temperatures (4 and -18 degrees C). Ying Yong Sheng Tai Xue Bao, 2004 Jun, 15(6), 1100 - 4 {Antibiotics production by bacterial agents and its role in biological control}; Wang G et al.; Using bacteria to control plant diseases is one of the main strategies in plant protection, and its mechanism is commonly thought to be the production of antibiotics by bacteria . The produced antibiotics not only have structural diversity, but also have broad-spectrum activity against many pathogens . Experimental results showed that one kind of antibiotics could be produced by several bacterial strains, and one bacterial strain could also produced more than one kind of antibiotics . Recent development in molecular and bio-analytical techniques greatly promoted the research of bacterial bio-control, and the colonization survey of introducing bacterial strain to the rhizosphere and spermosphere of host plants . Besides bacterial genotypes, several biotic and abiotic factors including whether the pathogens existing or not, temperature, pH, carbon and nitrogen sources are also identified to affect the antibiotics production by bacteria . The authors illustrated some of the impeding problems in bacterial bio-control agents' application, and suggested that in the future research, more attention should be paid on developing mixed bio-control agent to avoid the anti-antibiotic activity of pathogens. Nurs Times, 2004 Aug 3-9, 100(31), 30 - 1 The rising incidence of antibiotic-resistant ESBL-producing E . coli; Shuttleworth A; Extended-spectrum beta-lactamase (ESBL) Escherichia coil produces enzymes that enable it to develop resistance to antibiotics . Its prevalence in the UK is increasing, and the Health Protection Agency is investigating whether it has contributed to a number of deaths . While many people may be asymptomatic carriers of ESBL-producing E . coli it can be extremely harmful to the very young, the very old and those with compromised health and other risk factors . Excellent infection control is necessary to prevent its spread in health care facilities, while restrictions on the use of antibiotics may be necessary to prevent its increasing resistance. Folia Med (Plovdiv), 2000, 42(4), 10 - 4 A fifteen-month survey of directly observed therapy--short course and antibiotic drug resistance in the region of Plovdiv; Torosyan AA et al.; OBJECTIVE: This study addresses the issue of antituberculosis drug resistance in a cohort of 213 patients from Plovdiv included in the pilot phase of a DOTS based project for a 15-month period . Between July 1 . 1998 and September 30, 1999, ninety three culture-positive patients participated in the study . 89 of them were tested for drug susceptibility to rifampicin, izoniazid, etambutol, and streptomycin . RESULTS: Resistance to at least one antituberculosis drug was established in 24.7% of the patients . Monoresistance was found in 13.5% of the cases . The median prevalence of combined resistance to rifampicin and isoniazid was 6.7% . The prevalence of resistance to rifampicin or isoniazid was 21.4% . Drug susceptibility testing results were obtained within 67 days . In 33% of the patients continuation treatment phase was initiated before drug susceptibility data were available . CONCLUSIONS: During the observed period a considerably high rate of drug resistant tuberculosis was registered among the patients included in the pilot phase of the program based on Directly Observed Therapy--Short Course . The percentage of resistance to R and/or I gives better information about the risk of inadequate treatment during the continuation treatment phase . The high percentage of this pattern of resistance in our region requires the continued use of four first-line drugs for therapy until the results of drug-susceptibility testing are received. FEMS Microbiol Lett, 2004 Sep 15, 238(2), 439 - 47 Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in streptomycetes; Huh JH et al.; The effect of S-adenosylmethionine (SAM) on the production of various antibiotics was investigated to determine whether SAM-dependent methylation is required in biosynthetic pathways of antibiotics . Pristinamycin II(B) and granaticin do not require SAM-dependent methylation in their biosynthesis pathways, and production of these two antibiotics was increased about 2-fold when a low concentration (50 and 10 microM, respectively) of SAM was treated; in contrast, oleandomycin and avermectin B1a require SAM as a methyl donor in their biosynthesis, and production of these two antibiotics was increased 5-fold and 6-fold, depending on the SAM concentration within a certain range . We also found that the transcription of a pathway-specific regulator, gra-ORF9, was activated by exogenous SAM treatment . Production of oleandomycin and avermectin B1a was decreased by using a methyltransferase inhibitor, sinefungin, but the production levels of these antibiotics were restored to the control level by simultaneously adding SAM and sinefungin . Interestingly, we have found a similar stimulatory effect of S-adenosylhomocysteine (SAH), the methylation product of SAM, on antibiotic production in the four strains . Our results clearly demonstrate the widespread activation of antibiotic production using SAM in streptomycetes. Curr Opin Biotechnol, 2004 Aug, 15(4), 356 - 63 Three-dimensional structures of enzymes useful for beta-lactam antibiotic production; Barends TR et al.; Significant advances have been made in the structure-based engineering of enzymes useful for beta-lactam antibiotic production . Structure-based engineering of penicillin G acylase and cephalosporin acylase has resulted in improved enzymes for use in enzymatic production processes . The structures of many other enzymes that could be used in the production of beta-lactam antibiotics, such as enzymes from the beta-lactam biosynthetic pathway and beta-lactam antibiotic-converting enzymes, have been determined . The interest in these structures suggests that the future may see an even more extensive use of rationally engineered biocatalysts in antibiotic production than today. Clin Infect Dis, 2004 Aug 15, 39(4), 526 - 31 Epub 2004 Aug 03. Challenges in the design of antibiotic equivalency studies: the multicenter equivalency study of oral amoxicillin versus injectable penicillin in children aged 3-59 months with severe pneumonia; Hibberd PL et al.; The World Health Organization (WHO) recommends that children with severe pneumonia (characterized by cough or difficult breathing, as well as lower chest wall indrawing) be hospitalized and treated with parenteral penicillin . Oral amoxicillin, if equally effective for treating severe pneumonia, would address challenges associated with providing parenteral therapy, including risk of transmission of bloodborne pathogens from contaminated needles, exposure to nosocomial pathogens during hospitalization, inadequate access to health care facilities, and cost . The recently completed multicenter international trial of oral amoxicillin versus parenteral penicillin for treatment of severe pneumonia demonstrated the equivalency of these agents in children with severe pneumonia . This article focuses on the challenges of designing an equivalence study and the threats to the validity of the trial results, particularly the implications of the bias toward finding equivalence when subjects are unlikely to respond to either study therapy . These considerations have implications for use of the Amoxicillin Penicillin Pneumonia International Study (APPIS) results in clinical practice and for potential modification of WHO treatment guidelines. Clin Infect Dis, 2004 Sep 1, 39(5), 641 - 8 Epub 2004 Aug 16. Reduction in high rates of antibiotic-nonsusceptible invasive pneumococcal disease in tennessee after introduction of the pneumococcal conjugate vaccine; Talbot TR et al.; BACKGROUND: Invasive pneumococcal disease (IPD) is a burgeoning problem, with rates of antibiotic-nonsusceptible IPD, in particular, increasing during the past decade . One measure to combat IPD is vaccination with the recently introduced 7-valent pneumococcal conjugate vaccine (PCV) . METHODS: To evaluate the effects of the introduction of PCV in 2000 on the epidemiology of antibiotic-nonsusceptible IPD, a database of IPD cases from January 1995 through December 2002 identified through active surveillance in 5 Tennessee counties was examined . For each case, clinical data were collected, and antibiotic susceptibility testing and serotyping were performed on available isolates . RESULTS: Among children younger than 2 years, IPD rates peaked at 235 cases per 100,000 in 1999 before decreasing, after PCV licensure, to 46 cases per 100,000 in 2002 (P<.001) . The proportion of penicillin-nonsusceptible IPD isolates from this age group declined from 59.8% in 1999 to 30.4% in 2002 (P<.01) . After 2001, similar decreases in IPD rates and in the proportion of antibiotic-nonsusceptible isolates recovered were seen among persons aged 2 years and older (P<.01) . Rates of IPD due to PCV-associated serotypes declined after PCV introduction in all age groups (P<.001), whereas the rate of IPD due to nonvaccine serotypes increased among persons aged 2 years and older . CONCLUSIONS: In the 2 years since licensure, widespread PCV vaccination of children has resulted in dramatic declines in the proportion of antibiotic-nonsusceptible isolates in Tennessee . PCV vaccination of children also appears to be a highly effective method for reducing the burden of IPD in adults. Tidsskr Nor Laegeforen, 2004 Sep 9, 124(17), 2240 - 1 {Parents' attitude to physician's role in the prescription of antibiotics to their children}; Nordlie AL et al.; BACKGROUND: Most children in day care get infections and are given antibiotics . In physicians' view, the main reason for excessive use is pressure exerted on them by anxious parents . We studied parents' view of physicians' influence on the use of antibiotics . MATERIAL AND METHOD: 563 parents (50%) in 22 day care centers returned a questionnaire about their children's infections, use of antibiotics, and their experience with the doctors treating their child . RESULTS: 70% of parents had confidence in physicians' decisions . Confidence was significantly higher in doctors that they regularly consulted than in others (p = 0.001) . 33% had moved on to a new physician on account of too much use of antibiotics (p < 0.05); these parents' children had received more antibiotics than other children (p < 0.05) . Parents were dissatisfied with the time set aside for the consultation and with doctors' information and follow up . They expected advice and guidance, not necessarily a prescription . 47% thought that too much antibiotics are prescribed . Satisfaction was associated with less antibiotics for their own child (p < 0.001) . Some parents regarded the prescription of antibiotics as doctors' way of saving time and bringing the consultation to an end . INTERPRETATION: Parents are sceptical of the use of antibiotics in children . More time set aside for the consultation is significantly associated with less use of antibiotics . Better doctor-parent communication may reduce excessive use. Tidsskr Nor Laegeforen, 2004 Sep 9, 124(17), 2229 - 31 {Parents' attitudes to the prescription of antibiotics to children}; Nordlie AL et al.; BACKGROUND: Most children in day care get infections and are prescribed antibiotics . We studied parents' attitude towards such prescription . MATERIAL AND METHODS: Parents (563 out of 1126 surveyed) in 22 day care centres returned a questionnaire on factors in their own situation and in their day care centre with impact on the use of antibiotics . RESULTS: Parents above 30 years of age, well educated and knowledgeable about antibiotics were the most sceptical of such treatment . A negative attitude on the part of employers and colleagues towards absence from work led to more use of antibiotics (p < 0.01) . Children in single-parent homes were given more antibiotics than those in two-parent homes (p < 0.05) . Help from relatives led to less use of antibiotics (p < 0.01) . Sick children went to day care in 16% of cases; 57% of those taking antibiotics still went to day care . INTERPRETATION: Parents' situation may influence the use of antibiotics in children . Too many children are taking antibiotics and still go to day care . Support in the workplace, from relatives and from friends may give parents a better chance of staying at home with a sick child, thus preventing the spread of infections and cut down on the use of antibiotics. Enferm Infecc Microbiol Clin, 2004 Aug-Sep, 22(7), 385 - 9 {Analysis of antibiotic use in the Community of Valencia (2000-2002)}; Pedrera V et al.; OBJECTIVE: To quantify antibiotic prescriptions in the Autonomous Community of Valencia in the years 2000-2002 and analyze the differences in antibiotic use among 20 Valencian Community health areas . METHODS: Retrospective observational population study (3,983,464 inhabitants) of prescriptions recorded in Valencian Community pharmacies during the period 2000-2002 . We calculated defined daily doses per 1000 inhabitants and day (DHD), for the population without pharmaceutical fees (e.g . pensioners), the population with pharmaceutical fees (e.g . actively working) and the total population . The antibiotics analyzed belonged the J01 group (ATC/DDD classification) . RESULTS: Antibiotic consumption was 26.47 DHD in 2000, 23.56 DHD in 2001 and 23.48 DHD in 2002 . The most frequently prescribed drug groups included: broad-spectrum penicillins (J01C) 11.8 DHD, macrolides (J01F) 5.6 DHD, and other beta-lactams (J01D) 3.95 DHD . There was considerable variation between the population without pharmaceutical fees and the population with pharmaceutical fees: JO1C (DHD 18.49 vs . 9.73), JO1F (11.06 vs . 3.84) and quinolones (J01M) (9.16 vs . 1.22) (p < 0.05) . There was also substantial variation between areas, both overall and by groups (p < 0.05): J01C 6.36 DHD to 12.14 DHD; (J01F), 3.78 DHD to 6.08 DHD; (J01D), 2.28 DHD to 4.65 DHD, and (J01M) 2.39 DHD to 3.6 DHD . CONCLUSIONS: There was a slight trend to decreasing antibiotic use in the Community of Valencia over the period of 2000-2002 . The population without pharmaceutical fees showed much higher antibiotic use than those with pharmaceutical fees, and there was considerable variation in prescriptions between the different public health care areas. Br J Gen Pract, 2004 Sep, 54(506), 659 - 62 C-reactive protein measurement in general practice may lead to lower antibiotic prescribing for sinusitis; Bjerrum L et al.; BACKGROUND: Symptoms of bacterial sinusitis overlap with viral sinusitis, and it is difficult to distinguish between the two conditions based only on a clinical examination . Uncertain diagnosis results in the significant overuse of antibiotics, which is considered to be one of the most important reasons for development of bacterial resistance to antibiotics . A raised C-reactive protein (CRP) level is an indicator of bacterial infection and the CRP rapid test has been shown to be useful for the diagnosis of bacterial sinusitis in general practice . AIMS: To examine whether general practitioners (GPs) who use the CRP rapid test in their practice have a lower antibiotic prescribing rate for sinusitis than GPs who do not use the test . DESIGN OF STUDY: Observational design . SETTING: General practice in Denmark . METHOD: A group of GPs registered all contacts (n = 17 792) with patients who had respiratory tract infections during a 3-week period between 1 November 2001 and 31 January 2002 . GPs who used a CRP rapid test were compared with GPs who did not, and the treatment of their patients (n = 1444) with suspected sinusitis was compared . RESULTS: A CRP rapid test was used by 77% (n = 281) of the GPs . In the group of GPs using a CRP rapid test, the rate of antibiotic prescribing was 59% (95% confidence interval {CI} = 56 to 62) compared with 78% (95% CI = 73 to 82) in the group of GPs who did not use a CRP test . Performing a CRP rapid test was the factor that exerted the greatest influence on whether the patients were prescribed antibiotics, and the level of CRP had a strong influence on the prescribing rate . CONCLUSION: The CRP rapid test has a substantial influence on the treatment of sinusitis, and implementing the test in general practice may lead to a reduction in antibiotic prescribing to patients with sinusitis. Electrophoresis, 2004 Aug, 25(16), 2825 - 9 A simplified synthesis of polymeric nonparticulate stationary phases with macrocyclic antibiotic as chiral selector for capillary electrochromatography; Kornysova O et al.; A simplified approach to synthesize nonparticulate (continuous or monolithic) beds with embedded vancomycin chiral selectors for capillary electrochromatography is proposed . In the present approach, N,N'-diallyltartardiamide monomer with diol functionality is used, which can be readily converted to aldehyde groups via periodate treatment . Parallel to the activation of the polymeric matrix for covalent attachment of vancomycin, the periodate treatment has shown secondary effects on the polymeric bed morphology, namely the increase of the average pore size and porosity of the skeleton . Inversed size-exclusion chromatography was applied to characterize porosimetric properties of the capillary columns before and after the periodate treatment . Electroosmotic and enantioselective properties of the nonparticulate beds synthesized are presented . The approach is of more general interest attaching different affinity groups to the polymeric matrix and/or enhancing the accessibility to the active sites, for instance, in the molecular imprinting technique. J Mater Sci Mater Med, 2002 Dec, 13(12), 1251 - 7 Acrylic-phosphate glasses composites as self-curing controlled delivery systems of antibiotics; Fernandez M et al.; New antibiotic delivery systems based on self-hardening methyl methacrylate (MMA)/polymethyl methacrylate (PMMA) systems and phosphate glasses (PG) in the system P(2)O(5)-CaO-Na(2)O have been developed . Self-curing formulations were prepared by mixing the solid component containing PMMA beads, different proportions of PG (30-70 wt %) and vancomycin (5 wt %) as antibiotic, with the liquid component made of MMA monomer . Dough and setting times increased with the content of PG but peak temperature decreased to values well below to guarantee the chemical stability of the antibiotic drug, gentamicin or vancomycin . Mechanical properties of the PMMA/PG composites were evaluated in compression test giving rise to values of compressive strength in the range of 100 MPa . The release of vancomycin was analyzed in vitro by immersion of samples in phosphate buffer of pH=7.4 . Release profiles were influenced by the content of PG present in the cement . An initial burst of drug release was observed in all cases . The composites with 70 wt % PG released nearly the total amount of drug loaded in a period of 45 days, and those containing 60 wt % PG released the 70% of the vancomycin in the same period of time . However, either the control of the composite with 30 wt % PG released only the 30% of the drug in 10-15 days . The surface of the drug-loaded composites before and after release experiments was analyzed by ESEM . The deposition of some aggregates at certain points of the surface was detected for the specimens immersed in buffer phosphate after 45 days . This material was characterized by FTIR and Raman spectroscopy as an amorphous phosphate formed by calcium ortho and pyrophosphates, and indicates an interaction between the hydrated layer at the place of the glass and the surrounding medium. J Mater Sci Mater Med, 2002 Oct, 13(10), 973 - 8 The in vitro antibiotic release from anti-washout apatite cement using chitosan; Takechi M et al.; The in vitro antibiotic release from anti-washout apatite cement using chitosan (aw-AC(chi)) was investigated in a preliminary evaluation . Flomoxef sodium was employed as the antibiotic and was incorporated into the powder phase aw-AC(chi) at up to 10% . The setting times were measured for aw-AC(chi) containing various amounts of flomoxef sodium . X-ray diffraction (XRD) analysis was also conducted for the identification of products . To evaluate the drug release profile, set aw-AC was immersed in saline and the released flomoxef sodium was determined at regular intervals . The setting time was prolonged slightly with the addition of flomoxef sodium . The difference at 10% flomoxef sodium (0% vs . 10%) was not significant (p>0.05), and can be negligible in clinic . The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-AC(chi) was reduced, even after 24 h, when the aw-AC(chi) contained flomoxef sodium at 8% or more . The flomoxef sodium release from aw-AC(chi) showed the typical profile observed in skeleton type drug delivery system (DDS) . Changing the concentration of chitosan can control the rate of drug release from aw-AC . Therefore, we conclude that aw-AC(chi) is a good candidate for potential use as a DDS carrier that may be useful in surgical operations. J Mater Sci Mater Med, 1999 Dec, 10(12), 743 - 6 Polymeric prodrugs of antibiotics with improved efficiency; Roseeuw E et al.; Macromolecular prodrugs of the antibiotic norfloxacin were prepared by coupling the drug via a peptide spacer onto a mannosylated dextran . The tetrapeptide gly-phe-gly-gly-gly-OMe was selected as substrate for lysosomal enzymes . The drug was coupled on the alpha-C of the terminal glycine . In vitro degradation studies demonstrated the release of the parent drug in the presence of cathepsin B . In vivo experiments on mice showed a promising therapeutic effect . Arch Environ Contam Toxicol, 2004 Jul, 47(1), 31 - 9 Effects of pig slurry on the sorption of sulfonamide antibiotics in soil; Thiele-Bruhn S et al.; Sorption of p-aminobenzoic acid (pABA) and five sulfonamide antibiotics to loess Chernozem topsoil amended with varied additions of pig slurry was investigated in batch trials . In unfertilized soil, partition coefficients (Kd) of sulfonamides ranged from 0.3 to 2.0 . Strong sorption nonlinearity (1/n = 0.5 to 0.8) was best fitted by the Freundlich isotherm (R2 = 0.7 to 1.0) and was indicative for specific sorption mechanisms . Adsorption to pig slurry was much stronger, and nondesorbable portions were increased compared with soil . However, in a mixture of soil and slurry (50:1 w/w), sorption of the antibiotics was significantly decreased at a lower concentration range of pABA and the sulfonamides . This was attributed to competitive adsorption of dissolved organic matter (DOM) constituents from manure . An increase in pig slurry amendment resulted in increased total organic matter, DOM concentration, and ionic strength, but pH decreased . As a result, the nonadsorbed portions of pABA, sulfanilamide, and sulfadiazine (logD(ow) < -0.4) ranged from 47% to 82% of the applied concentration in the differently manured substrates . Dissolved fractions of the antibiotics reached a maximum at a soil-slurry ratio of 9:1 and decreased with further addition of manure . This decrease was related to the formation of less-effective DOM associates in solution . The adsorbed and desorbed portions of the less-polar substances--sulfadimidine, sulfadimethoxine, and sulfapyridine (logD(ow) > 0.1)--remained nearly constant in the presence of increased manure input . The pH changes caused by manure amendment strongly affected ionisation status of the latter compounds, thus resulting in increased adsorption, which compensated the mobilizing effect of DOM . It is suggested that the effect of manure be considered in test methods to determine the soil retention of pharmaceutical substances. Drug Metab Dispos, 2004 Dec, 32(12), 1383 - 91 Epub 2004 Dec. Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats; Nakajima Y et al.; The Ministry of Health and Welfare, Japan banned coadministration of carbapenems, such as panipenem/betamipron (PAPM), meropenem (MEPM), and valproic acid (VPA) because clinical reports have indicated that the coadministration caused seizures in epileptic patients due to lowered plasma levels of VPA . In this study, we have clarified the mechanism of the drug-drug interaction using PAPM, MEPM, and doripenem {S-4661; (+)-(4R,5S,6S)-6-{(1R)-1-hydroxyethyl}-4-methyl-7-oxo-3-{{(3S,5S)-5-{(sulfamoylamino)methyl}-3-pyrrolidinyl}thio}-1-azabicyclo{3.2.0}hept-2-ene-2-caboxylic acid monohydrate}, a newly synthesized carbapenem . In vitro experiments using monkey liver slices suggested that the apparent synthetic rate of VPA glucuronide (VPA-G) increased in the presence of carbapenems . However, no such increase was observed in the experiment using monkey liver microsomes . Although no increase of uridine 5'-diphosphate D-glucuronic acid was found in monkey liver slices in the presence of carbapenems, potent inhibitory activity of carbapenems for the hydrolysis of VPA-G was found in monkey and rat liver homogenate . In vivo hydrolysis of VPA-G was clearly shown by the existence of VPA in plasma after dosing of VPA-G to rats, and its inhibition by carbapenems was also clearly shown by the negligible levels of VPA in rat plasma after coadministration of carbapenems and VPA-G . These results clearly indicate one of the important causes of drug interaction as follows: carbapenems would inhibit the hydrolytic enzyme, which is involved in the hydrolysis of VPA-G to VPA, resulting in a decrease of plasma concentration of VPA. Antibiot Khimioter, 2004, 49(3), 40 - 6 {An aromatic heptaene antibiotic levorin and its derivatives in muscle activity}; Kurbanov OG et al.; The review is concerned with the outlooks for the use of levorin, a membrane active and channel forming polyene antibiotic, and its alkyl derivatives in muscle activity . In complex with cholesterol and ergosterol, the aromatic heptaene antibiotic levorin forms structural ionic channels of the molecular size in the lipid and cell membranes . Levorin increases the membrane permeability for monosucrose and other neutral molecules as follows: H2O > urea > acetamide > glycerine > ribose > arabinose > glucose > saccharose . As a channel forming compound, levorin is able to induce in the cell membranes of the muscle fibres formation of additional channels permeable for the cations and to increase the flow of the energy dependent substrates to the cells and the outburst of the metabolites from them during intensive muscle activity . Levorin several times decreases the surface tension of aqueous solutions . In some models of experimental animals levorin promoted an increase of the blood fluidity and accelerated the blood stream in the blood vessels both in rest and in muscle activity . Physical load in a high power zone increases the intensity of lipid peroxidation that results in fatigue and lower physical efficiency . Possible prevention of an increase of the rate of free radical reactions by levorin and its alkyl derivatives providing higher antioxidant protection is discussed. J Arthroplasty, 2004 Sep, 19(6), 768 - 74 Antibiotic-loaded articulating cement spacer in the 2-stage exchange of infected total knee arthroplasty; Durbhakula SM et al.; An antibiotic-loaded articulating cement spacer (ALACS) was used in the 2-stage exchange of infected total knee arthroplasty . Specially designed molds produced articulating femoral and tibial spacer components . Twenty-four consecutive patients were followed for an average of 33 months (range, 28-51 months) . Two patients (8%) had a persistent infection after the first stage . Twenty-two patients (92%) underwent a successful 2-stage exchange . Minimal soft-tissue contracture and minimal bone loss were encountered during reimplantation . None of these patients developed a recurrent or persistent infection . The average postoperative knee flexion was 104 degrees (range, 89 degrees-122 degrees) . The average Hospital for Special Surgery score was 82 (range, 63-96) . The ALACS spacer preserved knee function between stages, resulting in effective treatment of infection, facilitation of reimplantation, and improved patient satisfaction. J Bone Joint Surg Am, 2004 Sep, 86-A(9), 1989 - 97 Two-stage revision hip arthroplasty for infection: comparison between the interim use of antibiotic-loaded cement beads and a spacer prosthesis; Hsieh PH et al.; BACKGROUND: A two-stage revision is a well-accepted method for the treatment of a deep infection of a hip with a joint implant . In the present study, the results associated with the interim use of antibiotic-loaded cement beads were compared with those associated with the interim use of an antibiotic-loaded cement prosthesis . METHODS: One hundred and twenty-eight consecutive patients who were managed with a two-stage revision hip arthroplasty for the treatment of an infection were followed clinically and radiographically for an average of 4.9 years . Cement beads were implanted following resection arthroplasty in the first seventy hips, and a custom cement prosthesis was implanted in the subsequent fifty-eight hips . RESULTS: There was no evidence of recurrent infection in 122 patients (95.3%); the infection-free rates in both groups were similar . The use of a spacer prosthesis was associated with a higher hip score, a shorter hospital stay, and better walking capacity in the interim period; a decreased operative time, less blood loss, and a lower transfusion requirement at the time of reimplantation; and fewer postoperative dislocations . CONCLUSIONS: The present study supports the safety and efficacy of the routine use of an antibiotic-loaded cement prosthesis in the interim between the stages of a two-stage revision procedure for the treatment of an infection at the site of a hip arthroplasty. Obes Surg, 2004 Aug, 14(7), 970 - 4 Prevention of deep wound infection in morbidly obese patients by infusion of an antibiotic into the subcutaneous space at the time of wound closure; Alexander JW et al.; BACKGROUND: Wound infections have been reported to occur in as many as 15% of wounds following the open procedure for gastric bypass in morbidly obese patients, resulting in significant disability, an increased health-care expenditure, and even death . METHODS: This study was performed to assess the potential for reduction of wound infection in patients undergoing open gastric bypass by using a multimodal application of measures including infusion of an antibiotic (kanamycin) into the wound after closure and allowing it to dwell for 2 hours . Follow-up was for a minimum of 6 weeks . RESULTS: Of 400 consecutive evaluable patients, none had a wound infection which started in the subcutaneous fat or fascia . One patient had a stitch abscess, two had superficial infections secondary to wound separation after suture removal, and one had infection after spontaneous evacuation of a seroma . CONCLUSION: Using an infusion of kanamycin into the wound and allowing it to dwell for a 2-hour period, along with other standard preventive measures, eliminated primary deep subcutaneous and fascial wound infections after open gastric bypass procedures. Org Biomol Chem, 2004 Sep 7, 2(17), 2411 - 4 Epub 2004 Aug 04. Biosynthesis of cervimycin C, an aromatic polyketide antibiotic bearing an unusual dimethylmalonyl moiety; Herold K et al.; Cervimycin C is the major component of an antibiotic complex produced by Streptomyces tendae HKI-179 consisting of a tetracycline-type aglycon, six tridesoxysugars and a rare dimethylmalonyl moiety . The biosynthetic origin of cervimycin was studied by molecular studies and feeding experiments, which reveal that the dimethylmalonate unit is not derived from malonate, but from valine . Anesthesiol Clin North America, 2004 Sep, 22(3), 473 - 91 Perioperative antibiotics and practice: little things that make a big difference; Keegan MT et al.; Perioperative antibiotic administration and anesthetic practice have major impacts on infectious complications . Anesthesiologists need to place high importance on perioperative antibiotic administration to allow patients to receive optimal benefit from this therapy and to minimize risk . Many aspects of perioperative care ranging from thermoregulation to glycemic control may have profound longterm affects on infection rate and thereby patient outcome. Int J Antimicrob Agents, 2004 Sep, 24(3), 247 - 53 Macrolide antibiotics induce apoptosis of human peripheral lymphocytes in vitro; Ishimatsu Y et al.; We previously reported that long-term administration of macrolides (MCL) reduced the number of lymphocytes in bronchoalveolar lavage fluid (BALF) of patients with chronic lower respiratory tract disease . To investigate the anti-inflammatory activity of macrolides, we evaluated their effect on apoptosis of lymphocytes isolated from human peripheral blood . Lymphocytes treated with clarithromycin, azithromycin and josamycin at a final concentration of 200 microg/ml showed positive staining for Annexin V, Fas and Fas ligand using flow cytometry with time at 12-72 h, while other antibiotics did not . Our results suggest that macrolides induce apoptosis of lymphocytes through Fas-Fas ligand pathway and could potentially reduce the number of lymphocytes in the lungs of patients with chronic lower respiratory tract disease. Bioorg Med Chem Lett, 2004 Sep 20, 14(18), 4783 - 9 Formation of squaric acid amides of anthracycline antibiotics . Synthesis and cytotoxic properties; Tevyashova A et al.; The reaction of the anthracycline glycoside antibiotics 1-3 with the squaric acid ester 4 gave the squaric acid amide esters 5-7 under neutral conditions, whereas over pH7 the products are the symmetric diamides (8, 9, 11, and 12) . Of the prepared compounds 11 was the most active on MCF-7 human mammary adenocarcinoma cells. J Vet Intern Med, 2004 Jul-Aug, 18(4), 499 - 504 Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs; Hostutler RA et al.; Canine histiocytic ulcerative colitis (HUC) is characterized by colonic inflammation with predominantly periodic acid-Schiff (PAS)-positive macrophages . The inflammation results in colonic thickening, ulcerations, and distortion of normal glandular architecture . Resultant clinical signs consist of chronic large bowel diarrhea, tenesmus, and marked weight loss, and the disease frequently results in euthanasia . Conventional therapy consists of some combination of prednisone, azathioprine, sulfasalazine, and metronidazole . Nine dogs (8 Boxers and 1 English Bulldog) with histologic confirmation of HUC were treated with antibiotic therapy (either with enrofloxacin alone or in combination with metronidazole and amoxicillin) . Clinical signs, physical examination findings, laboratory abnormalities, and the histologic severity of the disease were evaluated . Four of the 9 dogs had been treated previously with conventional therapy and had failed to respond favorably; then, these dogs were placed on antibiotic therapy (enrofloxacin, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3) and had resolution of clinical signs within 3-12 days . Five dogs were treated solely with antibiotic therapy (enrofloxacin, n = 1; enrofloxacin and metronidazole, n = 1; enrofloxacin, metronidazole, and amoxicillin, n = 3), and clinical signs resolved in 2-7 days . Repeated biopsy specimens were obtained from 5 dogs after treatment, and all showed marked histologic improvement . The increase in body weight after treatment was statistically significant (P = .01) . Three dogs currently are not on any treatment and have had resolution of clinical signs for up to 14 months . These observations suggest that an infectious agent responsive to antibiotics plays an integral role in the clinical manifestation of canine HUC, and they support the use of antibiotics in its treatment. Infez Med, 2004 Jun, 12(2), 132 - 5 Antibiotic usage and costs in the community; Karatas H et al.; A prospective study was designed in order to determine to what extent antibiotics are used in treating community-acquired infections and their costs . Between February and July 2001 a total of 43,011 prescriptions from a representative sample of pharmacies in the city of Denizli (Turkey) were evaluated during the study period . Antibiotics accounted for 16.4 % of total prescriptions and 30.8% of the market value of drugs . Penicillins (49.7%), followed by cephalosporins (17.3%), macrolides (9.5%), and aminoglycosides (7.6%) were the most frequently prescribed antibiotics during the study period . The economic burden of antibiotic usage in the community is found higher than in developed countries . In order to reduce this cost the proper use of antibiotics is a matter of urgency Orthopedics, 2004 Jul, 27(7), 709 - 12 The antibiotic cement nail for infection after tibial nailing; Madanagopal SG et al.; This article introduces the antibiotic-impregnated cement nail for the treatment of tibial shaft fracture infection and outlines the technique regarding its placement. Ann Univ Mariae Curie Sklodowska {Med}, 2003, 58(1), 444 - 51 Evaluation of an anti-chlamydial antibiotic therapy influence on asthma patients; Gryglicka B et al.; Chlamydia pneumoniae is one of the most frequent pathogens causing airways infections . Contribution of chronic chlamydial infection to the following diseases: asthma, POChP, coronary heart disease, abdominal aortic aneurysm, is particularly interesting . The connection between such infection and bronchial asthma was described in the literature in 1991 . C . pneumoniae often causes asthma exacerbation; it is suggested that it also may be an etiologic factor of the disease . In a group of 55 subjects with chronic, stable bronchial asthma treated in the Pulmonary Department, serologic characteristic of C . pneumoniae infection was found in 34 patients (61,8%) . Thirteen of these subjects agreed to participate in the study . They were divided into two groups; placebo was administered to the first one and azithromycin in a dose of 1000 mg once a week--to the other one . The research was conducted using the double blind trial method . Anti-chlamydial antibody level was evaluated before and after treatment . Spirometry tests as well as subjective estimation of physical fitness and dyspnoea degree were also determined . In comparison with 'the placebo group', statistically significant improvement in respiratory parameters 'in the treated group' was not ascertained. Pediatr Nurs, 2004 May-Jun, 30(3), 200 - 2 Antibiotic sampling from central venous catheters versus peripheral veins; McBeth CL et al.; This study was developed to determine if there are statistically or clinically significant differences in antibiotic levels of blood samples obtained from a central venous catheter (CVC) versus a peripheral vein . Currently there is limited and contradictory information comparing aminoglycoside levels drawn from a central line used for antibiotic infusions versus a separate peripheral blood draw . In this study antibiotic levels drawn from a central line were compared with levels drawn simultaneously from a peripheral vein . Significant clinical and statistical differences were identified based on the type of central catheter in place. Methods Mol Biol, 2005, 286, 191 - 202 Selectable markers: antibiotic and herbicide resistance; Goodwin JL et al.; The low efficiencies of most plant transformation methods necessitate the use of selectable marker genes to identify those cells that successfully integrate and express transferred DNA . Genes conferring resistance to various antibiotics or herbicides are commonly used in laboratory transformation research . They encode proteins that detoxify corresponding selection agents and allow the preferential growth of transformed cells . This chapter describes the application of two selection systems on the transformation of wheat . One is based on the nptII gene and corresponding aminoglycoside antibiotics, the other is based on the bar gene and corresponding glufosinate ammonium herbicides. World J Gastroenterol, 2004 Sep 15, 10(18), 2632 - 6 Mitotic cell death in BEL-7402 cells induced by enediyne antibiotic lidamycin is associated with centrosome overduplication; Liang YX et al.; AIM: Mitotic cell death has been focused on in tumor therapy . However, the precise mechanisms underlying it remain unclear . We have reported previously that enediyne antibiotic lidamycin induces mitotic cell death at low concentrations in human epithelial tumor cells . The aim of this study was to investigate the possible link between centrosome dynamics and lidamycin-induced mitotic cell death in human hepatoma BEL-7402 cells . METHODS: Growth curve was established by MTT assay . Cell multinucleation was detected by staining with Hoechst 33342 . Flow cytometry was used to analyze cell cycle . Aberrant centrosomes were detected by indirect immunofluorescence . Western blot and senescence-associated beta-galactosidase (SA-beta-gal) staining were used to analyze protein expression and senescence-like phenotype, respectively . RESULTS: Exposure of BEL-7402 cells to a low concentration of lidamycin resulted in an increase in cells containing multiple centrosomes in association with the appearance of mitotic cell death and activation of SA-beta-gal in some cells, accompanied by the changes of protein expression for the regulation of proliferation and apoptosis . The mitochondrial signaling pathway, one of the major apoptotic pathways, was not activated during mitotic cell death . The aberrant centrosomes contributed to the multipolar mitotic spindles formation, which might lead to an unbalanced division of chromosomes and mitotic cell death characterized by the manifestation of multi- or micronucleated giant cells . Cell cycle analysis revealed that the lidamycin treatment provoked the retardation at G2/M phase, which might be involved in the centrosome overduplication . CONCLUSION: Mitotic cell death and senescence can be induced by treatment of BEL-7402 cells with a low concentration of lidamycin . Centrosome dysregulation may play a critical role in mitotic failure and ultimate cell death following exposure to intermediate dose of lidamycin. Infect Dis Clin North Am, 2004 Sep, 18(3), 533 - 49, viii Antibiotic agents in the elderly; Stalam M et al.; Diagnosis and treatment of infections in the elderly is challenging and complicated because of age-related physiologic changes and lack of classical clinical symptoms . Elderly patients are more vulnerable to infections because of their underlying diseases . This article reviews the pharmacologic issues in treating the elderly with antibiotics, the most frequently encountered infections in this patient population, and the suggested antibiotic regimens . The discussion also includes the special challenges of treating these most frequently encountered infections in the elderly who reside in long-term care facilities. Photochem Photobiol . 2004 Apr 1; {Epub ahead of print} Spectroscopic Properties of Various Quinolone Antibiotics in Aqueous-Organic Solvent Mixtures; Park HR et al.; The spectroscopic properties of Enoxacin (ENO), Oxolinic acid (OXO) and Nalidixic acid (NAL) were studied in various H2O- CH3OH and H2O-CH3CN mixed solvents because these solvents were thought to behave as a biological mimetic system . ENO have piperazinyl group but OXO and NAL do not have this substituent . The fluorescence emission spectra of ENO were very sensitive to the composition of the solvents . In the Lippert-Mataga analysis of the steady-state fluorescence data, clear reverse solvatochromism was exhibited for ENO in both mixed solvents . This observation can be explained using the excited state twisted intramolecular charge transfer (TICT) from the nitrogen of the piperazinyl group to the keto oxygen . Theoretical calculations further support this observation . The nonradiative and radiative rate constants of these molecules were analyzed as a function of dipolarity-polarizability (pi*) and hydrogen bond donor acidity (alpha) of the mixed solvents . These results for ENO were consistent with the suggested mechanism of the TICT very well . The influence of bulk dielectric effect was more significant relative to the specific hydrogen-bonding interactions . The emission spectra of OXO and NAL do not exhibit any characteristic responses to the properties of the solvent. Scand J Infect Dis, 2004, 36(6-7), 450 - 2 Self-medication with antibiotics in a Swedish general population; Svensson E et al.; To assess the extent of antibiotic self-medication in a Swedish population, a postal questionnaire was distributed to 1000 randomly selected subjects . The antibiotics used were in all but 3 cases reported to have been obtained with a prescription . Thus, prescribers are the primary target for interventions to optimize antibiotic use. Acta Chir Iugosl, 2003, 50(4), 123 - 8 {Antibiotics in the prevention of the surgical site infection in orthopedic surgery}; Vucetic S et al.; Surgical site infection is an actual problem of orthopaedic surgery . Despite considerable efforts that have been done during last several decades (e.g . improvements in surgical techniques, preoperative preparation of the surgical site, infection-control practice, use of preventive antibiotics) surgical site infection still affects about 0.5-2% of patients after closed fracture surgery or insertion of prosthetic devices . They are associated with substantial morbidity and mortality . The adherence to the principles of rationale preventive antibiotic therapy has an important role in the prevention of the surgical infection . In addition, it is well known that inappropriate use of antibiotic promote development of resistance, superinfections and increase the cost of the treatment . This paper focuses on the basic principles of rational use of antibiotics, i.e . appropriate selection of drug, dose, and duration of treatment in the prevention of surgical site infections in orthopaedic surgery. JAMA, 2004 Aug 11, 292(6), 721 - 5 Feasibility of eliminating ocular Chlamydia trachomatis with repeat mass antibiotic treatments; Melese M et al.; CONTEXT: Mass antibiotic administrations for ocular chlamydial infection play a key role in the World Health Organization's trachoma control program . Mathematical models suggest that it is possible to eliminate trachoma locally with repeat mass treatment, depending on the coverage level of the population, frequency of mass treatments, and rate that infection returns into a community after each mass treatment . Precise estimates of this latter parameter have never been reported . OBJECTIVE: To determine the rate at which chlamydial infection returns to a population after mass treatment and to estimate the treatment frequency required for elimination of ocular chlamydia from a community . DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study of 24 randomly selected villages from the Gurage Zone in Ethiopia conducted February 2003 to October 2003 . A total of 1332 children aged 1 to 5 years were monitored for prevalence of ocular chlamydial infection pretreatment and 2 and 6 months posttreatment . INTERVENTIONS: All individuals older than 1 year were eligible for single-dose oral azithromycin treatment . Pregnant women were offered tetracycline eye ointment . MAIN OUTCOME MEASURES: Prevalence of ocular chlamydial infection, measured by polymerase chain reaction, in children aged 1 to 5 years, in each of 24 villages at each time point was used to estimate the rate of return of infection and the treatment frequency necessary for elimination . RESULTS: The prevalence of infection was 56.3% pretreatment (95% confidence interval {CI}, 47.5%-65.1%), 6.7% 2 months posttreatment (95% CI, 4.2%-9.2%), and 11.0% 6 months posttreatment (95% CI, 7.3%-14.7%) . Infection returned after treatment at an exponential rate of 12.3% per month (95% CI, 4.6%-19.9% per month) . The minimum treatment frequency necessary for elimination was calculated to be once every 11.6 months (95% CI, 7.2-30.9 months), given a coverage level of 80% . Thus, biannual treatment, already being performed in some areas, was estimated to be more than frequent enough to eventually eliminate infection . CONCLUSION: The rate at which ocular chlamydial infection returns to a community after mass treatment suggests that elimination of infection in a hyperendemic area is feasible with biannual mass antibiotic administrations and attainable coverage levels. J Dent, 2004 Sep, 32(7), 503 - 9 Pattern of antibiotic prescription in the management of oral diseases among dentists in Kuwait; Salako NO et al.; OBJECTIVES: The use and abuse of antibiotics have been of concern to the medical and the dental profession for sometime now, due mainly to the emergence of antibiotic-resistant bacteria . The objective of this project was to determine the rationale and the pattern of antibiotic prescription for dental management in Kuwait . METHODS: A questionnaire was distributed to 200 dental practitioners working in the Ministry of Health dental centers in Kuwait . The questionnaires sought answers to the clinical and non-clinical factors; signs, clinical conditions and dental treatment modalities for which the practitioners would prescribe antibiotics . RESULTS: Of the 200 questionnaires sent out, 168 (84%) respondents returned fully completed forms . A total of 107 (63.7%) of the respondents were males . Of respondents, 90% would prescribe antibiotics for patients with elevated body temperatures and evidence of systemic involvement, gross or diffuse facial swelling and closure of the eye due to inflammatory swelling . However, over 50% would prescribe antibiotics for cases with localized fluctuant swelling without any systemic involvement, while 59.6% would prescribe for patients with difficulty in swallowing as a result of an oral infection . Many respondents would consider antibiotic prescription for routine dental extraction, and for non-clinical reasons such as uncertainty of diagnosis, convenience, expectation of the patient and lack of time to treat immediately . Amoxicillin was the most frequently prescribed antibiotic . Higher knowledge regarding adequate indications for antibiotic use was associated with longer professional experience . CONCLUSIONS: The results of this analysis suggest that there is lack of uniformity in the rationale for antibiotic use among dental practitioners in Kuwait . There is an urgent need for the formulation of evidence-based guidelines, which should take into account the peculiar behavioral characteristics of the community. Pharmacotherapy, 2004 Jul, 24(7), 856 - 70 Likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group; Brackett CC et al.; Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic, sulfonamide-containing drugs persist and can complicate patients' drug therapy unnecessarily . No interaction between the human immune system and the sulfonamide functional group has been demonstrated . The immunologic determinant of type I, immediate hypersensitivity responses to sulfonamide antibiotics is the N1 heterocyclic ring . Nonantibiotic sulfonamides do not contain this structural feature . Non-type I hypersensitivity responses to sulfonamide antibiotics are largely attributable to reactive metabolites that may cause either direct cytotoxicity or immunologic response . Formation of these metabolites is a stereospecific process that occurs at the N4 amino nitrogen of the sulfonamide antibiotics, a structure also not found on any nonantibiotic sulfonamide drugs . The stereospecificity of these reactions implies that cross-reactivity with nonantibiotic sulfonamide-containing drugs is highly unlikely; this assertion is supported by recent literature . However, T-cell recognition of unmetabolized, nonhaptenated parent sulfonamide antibiotic appears to occur in a small subset of hypersensitive patients . Several of the severe cutaneous reactions associated with sulfonamide antibiotics are mediated by T cells . It is not known whether T-cell recognition of antibiotic is related to the sulfonamide functional group . Until the mechanism of this recognition is elucidated, cross-reactivity with nonantibiotic sulfonamides appears to remain at least theoretically possible. Acta Crystallogr D Biol Crystallogr, 1995 Nov, 51(Pt 6), 1084 - 5 Preliminary X-ray diffraction study of a new crystal form of C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C-1027 from Streptomyces globisporus; Motojima F; A new crystal form of C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C-1027 isolated from Streptomyces globisporus was obtained by the vapor-diffusion procedure using lithium sulfate as a precipitant . In the present crystallization, it is noteworthy that large-sized single crystals successfully grew from very small droplets (less than 1.01 micro l) . The present crystals belong to the trigonal system, space group P3(1)21 or P3(2)21 with cell dimensions of a = b = 62.6 and c = 54.2 A . Assuming that the asymmetric unit contains one molecule, the V(m) value is calculated as 2.9 A(3) Da(-1) . A total of 3654 independent reflections from two native crystals was obtained up to 2.5 A resolution with synchrotron radiation, the merging R factor being 0.097. Acta Crystallogr D Biol Crystallogr, 1993 Jul, 49(Pt 4), 372 - 4 Crystallization and preliminary X-ray diffraction studies of C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C-1027 from Streptomyces globisporus; Briozzo P; C-1027-AG, the apoprotein of the macromolecular antitumor antibiotic C- 1027, isolated from Streptomyces globisporus, was crystallized by the vapor-diffusion procedure using 2-methyl-2,4-pentanediol as a precipitant . The crystals belong to the orthorhombic system, space group P2(1)2(1)2(1), with unit-cell dimensions a = 55.1, b = 61.3 and c = 79.1 A . Assuming that the asymmetric unit contains two or three molecules, the V(m) value is calculated as 3.2 or 2.1 A(3) Da(-1), respectively . A total of 7630 independent reflections was obtained up to 2.5 A resolution with synchrotron radiation, the merging R factor being 0.077 for 24 713 measurements. Yakugaku Zasshi, 2004 Aug, 124(8), 469 - 79 {Metabolites produced by actinomycetes--antiviral antibiotics and enzyme inhibitors}; Uyeda M; In 1995, we discovered new antiherpetic antibiotics, called fattiviracins . The producing organism was classified as a strain belonging to Streptomyces microflavus . The strain produced at least 13 fattiviracin derivatives (FV-1 to FV-13) . Fattiviracins were obtained as a white amorphous powder, and their molecular weights are in the range of 1400 to 1500 . They are readily soluble in water, methanol, pyridine, and DMSO, but insoluble in other organic solvents . Fattiviracins have macrocyclic diesters formed by the binding of two trihydroxy fatty acids and two D-glucose residues in the molecule, and they can be divided into five families according to the length of the fatty acid moiety . Fattiviracins have potent activity against enveloped DNA viruses such as the herpes family, HSV-1, and VZV and enveloped RNA viruses such as influenza A and B viruses, and three strains of HIV-1, with EC(50) values on the order of a few micrograms per milliliter . The biosynthetic pathway of fattiviracins is also becoming clearer . Using bacitracin-resistant strains, enhanced and astringent production of fattiviracin was achieved . Fattiviracin FV-13, which has the longest fatty acid chains in the molecule, was dramatically enhanced by a C(55)-isoprenyl phosphate metabolism . In addition, we have screened various inhibitors of enzymes such as alkaline protease, glucosyltransferase, glucuronidase, phospholipase, deoxyribonuclease, DNA methyltransferase, and DNA topoisomerase . All the inhibitors we discovered are briefly summarized in this paper. BMJ . 2004 Aug 21;329(7463):431 . Epub 2004 Aug 05. Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial; Welschen I et al.; OBJECTIVES: To assess the effectiveness of a multiple intervention aimed at reducing antibiotic prescription rates for symptoms of the respiratory tract in primary care . DESIGN: Randomised controlled trial . SUBJECTS: Twelve peer review groups including 100 general practitioners with their collaborating pharmacists in the region of Utrecht, Netherlands . INTERVENTION: The intervention consisted of group education meetings, with a consensus procedure on indication for and type of antibiotics and with training in communication skills; monitoring and feedback on prescribing behaviour; group education for assistants of general practitioners and pharmacists; and education material for patients . The control group did not receive any of these elements . MAIN OUTCOME MEASURES: Antibiotic prescription rates for acute symptoms of the respiratory tract and patients' satisfaction . RESULTS: 89 general practitioners completed the study (89%) . At baseline, prescription rates for antibiotics for respiratory tract symptoms did not differ between intervention and control group (27% v 29%, respectively) . After nine months, the prescription rates in the intervention group fell to 23%, whereas the control group's rose to 37% (mean difference in change -12%, 95% confidence interval -18.9% to -4.0%) . Multilevel analysis confirmed the results of the unadjusted analysis (intervention effect -10.7%, -20.3% to -1.0%) . Patients' satisfaction was high and did not differ in the two groups at baseline or after the intervention . CONCLUSIONS: A multiple intervention reduced prescribing rates of antibiotics for respiratory tract symptoms while maintaining a high degree of satisfaction among patients . Further research should focus on the sustainability and cost effectiveness of this intervention. Anal Sci, 2004 Jul, 20(7), 1007 - 11 ppt level detection of samarium(III) with a coated graphite sensor based on an antibiotic; Ganjali MR et al.; N-{2-{4-{{{(Cyclohexylamino)carbonyl}amino}sulfonyl}phenyl}ethyl}-5-methyl pyrazine carboxamide (glipizid) was explored as an electro-active material for preparing a polymeric membrane-based sensor selective to samarium ions . The membrane incorporated 30% poly(vinyl chloride) (PVC), 53% benzyl acetate (BA), 11% glipizid and 6% sodium tetraphenyl borate . When coated on the surface of a graphite electrode, it exhibits Nernstian responses in the concentration range of 1.0 x 10(-5) to 1.0 x 10(-10) M, with a detection limit of 8.0 x 10(-11)M samarium . The electrode shows high selectivity towards samarium over several cations (alkali, alkaline earth, transition and heavy metal ions), and specially lanthanide ions . The proposed sensor has a very short response time (< 15 s), and can be used in a wide pH range for at least ten weeks . It was used as an indicator electrode in potentiometric titration of Sm(III) ions with an EDTA solution, and for determination of samarium in binary and ternary mixtures. Lakartidningen, 2004 Jul 8, 101(28-29), 2332 - 5 {Increasing incidence of ciprofloxacin resistant gonorrhea in Sweden . Choose a correct antibiotic and follow up the treatment!}; Berglund T et al.; The incidence of gonorrhoea has increased in Sweden and is now three times higher than in the middle of the 1990's . A remarkable increase of ciprofloxacin resistant gonorrhoea has been reported in Stockholm and other parts of Sweden during 2003 . Among men attending a clinic for homosexual men in Stockholm the ciprofloxacin resistant cases have increased from a low level to over 50% during the last year . Most of the homosexual men are exposed in Stockholm and one serotype is dominant . Also in the county of Gavleborg there has been an outbreak of ciprofloxacin resistant gonorrhoea among young heterosexual men and women . No resistance to cefixime, ceftriaxone and spectinomycin has been noted and these antibiotics are then a better first choice of treatment in a Swedish context. Inflamm Bowel Dis, 2004 May, 10(3), 318 - 20 Antibiotics should be used as first-line therapy for Crohn's disease; Greenberg GR; The etiology of Crohn's disease remains uncertain, and to date no therapy is curative . Recent experimental evidence suggests that an altered immune response to commensal enteric flora in a genetically susceptible host plays a key role in both the development and perpetuation of the intestinal inflammation of Crohn's disease . Thus, incorporation of antibiotics into the therapeutic armamentarium for Crohn's disease, either as first-line therapy or combined with immunomodulatory drugs, would seem to be a rational strategy . Indeed, most IBD clinicians would attest to the marked benefit of antibiotic therapy in individual patients . Skepticism surrounding this approach arises because evidenced-based analyses' show that the few clinical trials evaluating the efficacy of antibiotics for Crohn's disease have produced equivocal or negative results or have methodological deficiencies, including small number of patients and absence of a placebo group . However, by undertaking an analysis that integrates information from both basic and clinical spheres of study, the dichotomy between experimental and clinical observations tends to merge . This approach underscores certain key factors that determine an optimal response to antibiotics, emphasizes the requirement for assessment in well-defined subsets of patients, and leads to the conclusion that antibiotics do provide benefit for Crohn's disease. Anal Bioanal Chem . 2004 Jul 28; {Epub ahead of print} Stability of fluoroquinolone antibiotics in river water samples and in octadecyl silica solid-phase extraction cartridges; Turiel E et al.; Intensive use of antibiotics in human and veterinarian medicine and in industrial farming (food additives) has resulted in the transport of important quantities of the active ingredients to environmental waters . Environmental analysis usually requires sample storage for certain periods of time and, consequently, it is of great importance to know the stability of antibiotics in these kinds of sample . Thus, in this work the stability in river water of oxolinic acid (Oxo) and ciprofloxacin (Cip), taken as representatives of fluoroquinolone and quinolone antibiotics respectively, has been evaluated . The stability of these compounds in river water has been studied both in containers and on C(18) solid-phase extraction cartridges (SPE) under different storage conditions (time, light, and temperature) . Data analysis revealed that Cip and Oxo have different degradation profiles with different degradation kinetics in river water . It was also concluded that these antibiotics are stable both in the containers and on SPE cartridges for at least 2 weeks at ambient temperature, and stability can be increased substantially if samples are stored at low temperatures (4 and -18 degrees C). No Shinkei Geka, 2004 May, 32(5), 457 - 62 {Nocardial brain abscess: surgery and postoperative antibiotic therapy}; Yoneyama T et al.; Nocardial infections in an immunocompromised host have been increasingly reported . Nocardial brain abscess, the most common presentation of nocardiosis in the central nervous system, is associated with a high mortality rate because of its delayed diagnosis and its unresponsiveness to the usual antibiotic therapy . We report four patients who experienced a long-term cure of nocardial brain abscess due to treatment by a combination of surgery and postoperative antibiotic therapy; 1 man and 3 women, ages ranging from 43 to 67 years old . Two patients were associated with systemic lupus erythematosus and two with autoimmune hemolytic anemia . Patients underwent surgical aspiration and drainage of brain abscess . Nocardia was identified from the aspirated specimen and postoperative antibiotic therapy for 5-6 weeks was performed using effective antibiotic agents; sulfamethoxazole/trimethoprim (ST), imipenem/cilastatin and minocycline (MINO) in Case 1, ST and MINO in Case 2, erythromycin in Case 3, and panipenem/betamipron and cefotaxime in Case 4 . Case 3 and Case 4 with multilobulated brain abscess underwent total excision of the brain abscess . All patients showed successful cure of nocardial brain abscess with no recurrence for the period of 1-8 years . The combination of surgery and postoperative antibiotic therapy provides a good prognosis for nocardial brain abscess. Nat Struct Mol Biol, 2004 Sep, 11(9), 888 - 93 Epub 2004 Aug 01. An antibiotic factory caught in action; Keatinge-Clay AT et al.; The synthesis of aromatic polyketides, such as actinorhodin, tetracycline and doxorubicin, begins with the formation of a polyketide chain . In type II polyketide synthases (PKSs), chains are polymerized by the heterodimeric ketosynthase-chain length factor (KS-CLF) . Here we present the 2.0-A structure of the actinorhodin KS-CLF, which shows polyketides being elongated inside an amphipathic tunnel approximately 17 A in length at the heterodimer interface . The structure resolves many of the questions about the roles of KS and CLF . Although CLF regulates chain length, it does not have an active site; KS must catalyze both chain initiation and elongation . We provide evidence that the first cyclization of the polyketide occurs within the KS-CLF tunnel . The mechanistic details of this central PKS polymerase could guide biosynthetic chemists in designing new pharmaceuticals and polymers. Hum Reprod, 2004 Oct, 19(10), 2325 - 33 Epub 2004 Jul 29. A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations; Primi MP et al.; BACKGROUND: Assisted hatching (AH) techniques, designed for facilitating the embryo escape out of the zona pellucida (ZP) have been used in IVF centres since 1992 . The initial indications for AH were patient's age, ZP thickness, high basal FSH and repeated IVF failures . Several retrospective and prospective studies assessing AH in these indications have given disparate results . Our aims were to evaluate the benefits of AH and immunosuppressive/antibiotic treatment (IA) in patients with either a poor prognosis of success, previous implantation failures or transfers of cryopreserved embryos . METHODS: Four IVF centres allocated 426 patients, randomized for AH and IA, into four groups of AH indications between 1997 and 1999 . AH was performed with a diode laser . ZP thickness, opening size and embryo score were recorded . Outcome measures were implantation and delivery rates . RESULTS: Patients coming for a first or third transfer of cryopreserved embryos and poor prognosis patients admitted for a first trial did not benefit from AH . Even patients with repeated implantation failures of fresh embryos did not gain significantly from AH . CONCLUSIONS: Among AH indications, absence of implantation after several transfers of good quality embryos remains the strongest patient selection criterion . Prescription of an immunosuppressive/antibiotic treatment is essential. Am J Hematol, 2004 Aug, 76(4), 319 - 29 Increasing dose intensity of anthracycline antibiotics improves outcome in patients with acute myelogenous leukemia; Novitzky N et al.; To understand the effect of dose concentration in the overall survival of AML, we conducted a study on the efficacy and toxicity of a drug combination where the dose of daunorubicin was intensified . For this analysis, the outcome of patients entered into two consecutive prospective trials was compared . Inclusion criteria in both arms were identical and consisted of primary AML in adults . Treatment protocol for Cape Town Regimen 4 (CTR-IV) comprised of cytarabine infusion (100 mg/m(2)) and etoposide (100 mg/m(2)), injection daily for 7 days in combination with daunorubicin (45 mg/m(2)) on days 1, 2, and 3 . Patients achieving remission were given two further courses of the same chemotherapy and received allogeneic or autologous transplantation . CTR-V was a similar treatment program, except that daunorubicin was escalated on days 1, 2, and 3 to 75 mg/m(2) during induction and to 60 mg/m(2) during a single consolidation . Patients were also offered stem cell transplantation . Between 1990 and 1997, 78 patients (median age 33; range 13-67 years) fulfilled entry criteria and received CTR-IV . From 1998 onwards, 35 patients (median age 36; range 15-66 years) were prospectively enlisted into the CTR-V trial . The patient population in CTR-V had fewer Caucasian individuals (P = 0.02) and had significantly lower presentation hemoglobin (P = 0.0002) . Following initiation of induction chemotherapy, 40 patients failed to respond . Among these, 10 patients demised before day 28 . Another 30 (25/69 CTR-IV and 5/32 in CTR-V groups; P = 0.01) had leukemia that was resistant to chemotherapy, and all died . Remission was achieved in 59% of patients treated with CTR-IV and 77% of those receiving CTR-V (P = 0.03) . CR occurred with a single course in 64% versus 88% (P = 0.02), respectively . There were no differences in the toxicity profile between these two combinations . Disease recurred in 50% and 28% (P = 0.07) of patients . For the 113 individuals, median follow up is 254 (range 19-4,451) and 304 (12-1,702; P = 0.03) days . Survival is 23% and 40%, respectively, favoring patients treated with CTR-V (log rank; P = 0.03) . Cox regression analysis showed that treatment group (P < 0.001), FAB type, hemoglobin level, and platelet count were independent factors for response to chemotherapy . Older age and not undergoing myeloablative therapy were the only adverse factors for survival . We conclude that increase in the treatment dose of daunorubicin in patients with AML led to a higher remission rate, particularly with a single course of chemotherapy and had an equivalent toxicity profile . This therapeutic modification is also likely to result in substantial reduction in patient stay in hospital and in the overall expenditure . J Antimicrob Chemother, 2004 Sep, 54(3), 661 - 72 Epub 2004 Jul 28. Optimizing antibiotic prescribing for acute cough in general practice: a cluster-randomized controlled trial; Coenen S et al.; OBJECTIVES: To assess the effect of a tailored professional intervention, including academic detailing, on antibiotic prescribing for acute cough . METHODS: In a cluster-randomized controlled before and after study 85 Flemish GPs included adult patients with acute cough consulting in the periods February-April 2000 and 2001 . The intervention consisted of a clinical practice guideline for acute cough, an educational outreach visit and a postal reminder to support its implementation in January 2001 . Antibiotic prescribing rates and patients' symptom resolution were the main outcome measures . RESULTS: Thirty-six of 42 GPs received the intervention and 35 of 43 GPs served as controls; 1503 patients were eligible for analysis . Only in the intervention group were patients less likely to receive antibiotics after the intervention {OR(adj) (95% CI)=0.56 (0.36-0.87)} . Prescribed antibiotics were also more in line with the guideline in the intervention group {1.90 (0.96-3.75)} and less expensive from the perspective of the National Sickness and Invalidity Insurance Institute {MD(adj) (95% CI)= Euro -6.89 {-11.77-(-2.02)}} . No significant differences were found between the groups for the time to symptom resolution . CONCLUSIONS: An (inter)actively delivered tailored intervention implementing a guideline for acute cough is successful in optimizing antibiotic prescribing without affecting patients' symptom resolution . Further research efforts should be devoted to cost-effectiveness studies of such interventions. J Am Acad Dermatol, 2004 Aug, 51(2 Suppl), S80 - 2 Beta-lactam antibiotic-induced pseudoporphyria; Phung TL et al.; A case of beta-lactam antibiotic-induced pseudoporphyria is presented . A 24-year-old African American woman with systemic lupus erythematosus and end-stage renal disease on hemodialysis developed tense bullae on her forehead and cheeks after exposure to ampicillin-sulbactam and cefepime . Histologically, the lesions were similar to porphyria cutanea tarda, but without the associated porphyrin abnormalities . The lesions resolved spontaneously on cessation of the antibiotics. J Anesth, 1991 Jan 1, 5(1), 1 - 9 The pre- and postjunctional components of the neuromuscular effect of antibiotics; Vizi ES et al.; The relative contributions of the pre- and postsynaptic components of the myoneural blocking effect of different antibiotics were studied using: (a) a radio-active method that measures selectively the Ca(2+)-dependent, stimulation evoked, quantally released, (3)H-acetylcholine ((3)H-ACh) from the mouse in vitro phrenic nerve-hemidiaphragm preparation without cholinesterase inhibition; (b) measurement of the force of contraction of the indirectly or directly stimulated muscle . The antibiotics studied (neomycin, polymyxin B and lincomycin), reduced the release of (3)H-ACh evoked by stimulation (18 trains of 40 shocks at 50 Hz) in a concentration dependent manner . While the inhibitory effect of neomycin was inversely related to {Ca(2+)}(o), that of lincomycin was moderately and that of polymyxin B was not affected by increasing {Ca(2+)}(o) from 0.75 to 5.0 mM . Similarly, the d-tubocurarine (d-Tc)-induced inhibition of the release of (3)H-ACh was independent of {Ca(2+)}(o) . The K-channel blocking agent, 4-aminopyridine (4-AP), enhanced the release of ACh in a concentration dependent manner and prevented the neuromuscular effect of neomycin . However, the neuromuscular effect of polymyxin B and of lincomycin was not affected by 4-AP . Atropine, enhanced the release of (3)H-ACh . Antibiotics, however, were still able to reduce the release of ACh when the negative muscarinic feedback mechanism of ACh release was eliminated by atropine . Our findings indicate that the antibiotics studied possess both pre- and postsynaptic effects . Presynaptically they reduce the evoked release of ACh; postsynaptically they inhibit muscle contractility . The rank order of presynaptic action is neomycin >polymyxin B >lincomycin.(Vizi ES, Chaudhry IA, Goldiner PL, et al.: The pre- and postjunctional components of the neuromuscular effect of antibiotics . J Anesth 5: 1-9, 1991) Proc Natl Acad Sci U S A, 2004 Aug 17, 101(33), 11980 - 5 Epub 2004 Jul 26. Toward the synthesis of the carbacylic ansa antibiotic kendomycin; Mulzer J et al.; The convergent synthesis of a benzofuran analog of the carbacyclic ansa compound kendomycin has been achieved by assembling three major fragments by means of epoxide opening and directed ortho lithiation . The crucial tetrahydropyran ring was formed by a highly stereoselective cationic cyclization . Analysis of all synthesized tetrahydropyran-arene compounds reveals a hindered sp(2)-sp(3) rotation, which results in rotational isomers or atropisomers affecting macrocyclization reactions . The latter could only be achieved by means of Horner-Wadsworth-Emmons olefination. Aten Primaria, 2004 Jul-Aug, 34(3), 128 - 33 {Consumption of antibiotics and their possible relationship with bacterial resistance in the "Costa de Ponent" health region: analysis of evolution through the initial and end periods of the last decade}; Sole Lopez J et al.; OBJECTIVE: To analyse antibiotic consumption (ABC) and its trend in primary care in an area with a high rate of bacterial resistance during the periods 1993-96 and 2000-02 . DESIGN: Comparative, retrospective analysis . SETTING: Costa de Ponent Health Region . Population in 1993-96 period was 1,158,098 inhabitants; in 2000-02 period, 1,188,007 inhabitants . PARTICIPANTS: Those patients in the Area who took AB during the periods under study . MEASUREMENTS: Data obtained from the appropriate records of the Catalan Health Service . Measurement of ABC was the Defined Daily Dose (DDD)/1000 inhabitants/day (DID) {criteria of the WHO Collaborating Centre for Drugs Statistics Methodology} . Trends were quantified as percentage increase or drop, comparing the 1993-96 and 2000-02 periods . The U Mann-Whitney test was used . RESULTS: Overall consumption was high, with a light fall from 17.049 DID during the first period to 15.826 DID in the second (-7.1%) . Amoxycillin increased from 4.878 DID (57.6%) to 6.19 DID (67.6%) (+26.8%), but amoxycillin-clavulanic did not rise . The percentages of macrolides, quinolones, cephalosporins, sulphonamides, and tetracyclines were higher in the first period . The variations in the consumption of clarithromycin, azithromycin, cefuroxime, cefixime, and ciprofloxacin between the two periods was the most notable point . CONCLUSIONS: Although overall ABC was high and in accord with the high rate of bacterial resistance in our area, a satisfactory evolutionary trend was found . The fall in consumption in the second period was not significant, but an appropriate modification in its profile was noted: domination of aminopenicillins and drop in macrolides, cephalosporins and fluorquinolones. Asian J Androl, 2004 Sep, 6(3), 249 - 57 Antibiotic-coated medical devices: with an emphasis on inflatable penile prosthesis; Abouassaly R et al.; One of the most serious complications associated with the use of the inflatable penile prosthesis is infection . This can lead to significant morbidity for the patient, as well as significant health care costs . A number of methods have been used in attempts at minimizing the infection risk, including applying an antibiotic coating to the medical devise . This review aims to evaluate the effectiveness of these products in preventing clinically significant infections. J Urban Health, 2004 Sep, 81(3), 498 - 504 Availability of antibiotics without prescription in New York City; Larson E et al.; Misuse of antibiotics in the community has been associated with emergence of increasingly antibiotic-resistant bacterial strains . Although antibiotics in the United States are to be prescribed by a health care provider, the extent to which they are obtained by other means is not known . The purpose of this article is to describe a survey of the availability of nonprescription antibiotics in neighborhood independent businesses in several Manhattan, New York, neighborhoods . A survey was conducted of 101 stores in three neighborhoods--one primarily Hispanic; one primarily black, non-Hispanic; and one primarily white, non-Hispanic . Antibiotics were available in all stores in the Hispanic neighborhood (n = 34), but in none of the others (P < .001) . If efforts to rationalize the use of antibiotics are to be successful, the beliefs and cultural norms of subpopulations must be considered, and interventions must be culturally relevant. Rev Panam Salud Publica, 2004 Jun, 15(6), 380 - 7 {Recommendation of the Brazilian Society of Pediatrics for antibiotic therapy in children and adolescents with community-acquired pneumonia}; Nascimento-Carvalho CM et al.; OBJECTIVE: To standardize the use of antibiotics to treat community-acquired pneumonia in children and adolescents in Brazil . METHODS: The following data sources were utilized: the Medline and LILACS (Literatura Latino-Americana e do Caribe em Ciencias da Saude) bibliographic databases; World Health Organization and Pan American Health Organization documents published between 1980 and 2002; Internet materials in Portuguese, Spanish, or English located using the search terms "pneumonia, child, adolescent, etiology, treatment"; and interviews with renowned experts in the field . RESULTS: Hospitalization is always required for children younger than 2 months of age . That age group should be treated with ampicillin and aminoglycosides or third-generation cephalosporins . Children older than 2 months must be hospitalized if there is severe pneumonia . Tachypnea should be used as the criterion to distinguish between acute respiratory infection and pneumonia . Pneumonia is considered to be very severe when there are seizures, sleepiness, stridor at rest, severe malnutrition, no ingestion of fluids, or signs of respiratory failure such as central cyanosis . Children who are 2 months of age or older may receive outpatient treatment with amoxicillin or penicillin G procaine . In the case of inpatient treatment, crystalline penicillin or ampicillin may be used for severe cases, and oxacillin and chloramphenicol or ceftriaxone for very severe cases . A macrolide, preferably erythromycin, should be employed when the etiologic agent is suspected to be Chlamydia trachomatis, C . pneumoniae, Mycoplasma pneumoniae, or Bordetella pertussis . CONCLUSIONS: The diagnosis of pneumonia and the need for hospitalization can be based on clinical assessment . The main antibiotics to be used are amoxicillin, penicillin, erythromycin, ampicillin, oxacillin, chloramphenicol, ceftriaxone, and aminoglycosides, depending on the age of the patient and the severity of the disease. Acta Crystallogr D Biol Crystallogr, 2004 Aug, 60(Pt 8), 1453 - 5 Epub 2004 Jul 21. Crystallization and initial X-ray analysis of phenoxazinone synthase from Streptomyces antibioticus; Smith AW et al.; Phenoxazinone synthase, an oligomeric multicopper oxidase produced by Streptomyces antibioticus, is responsible for the six-electron oxidative coupling of two molecules of 4-methyl 3-hydroxyanthraniloyl pentapeptide to form the phenoxazinone chromophore of the antineoplastic agent actinomycin D . Spectroscopic studies have shown that the enzyme contains one type I (blue) and three to four type II copper centers . However, the exact arrangement of the copper centers in this multicopper oxidase is unknown . As a first step towards determining the three-dimensional structure of the enzyme, phenoxazinone synthase has been crystallized . The hexameric form of phenoxazinone synthase was purified from 72 h cultures of S . lividans containing the plasmid pIJ702 . Purified hexamers were concentrated to 75 mg ml(-1) and used to grow two forms of crystals . Data collected from the two crystal forms were processed in two separate space groups . Crystals of both forms were grown at 288 K using the sitting-drop vapour-diffusion method . Native data sets extending to resolutions of 3.35 and 2.30 A have been collected and processed in space groups R32 and P1, respectively. Chem Biol, 2004 Jul, 11(7), 927 - 38 The biosynthetic gene cluster for a monocyclic beta-lactam antibiotic, nocardicin A; Gunsior M et al.; The monocyclic beta-lactam antibiotic nocardicin A is related structurally and biologically to the bicyclic beta-lactams comprised of penicillins/cephalosporins, clavams, and carbapenems . Biosynthetic gene clusters are known for each of the latter, but not for monocyclic beta-lactams . A previously cloned gene encoding an enzyme specific to the biosynthetic pathway was used to isolate the nocardicin A cluster from Nocardia uniformis . Sequence analysis revealed the presence of 14 open reading frames involved in antibiotic production, resistance, and export . Among these are a two-protein nonribosomal peptide synthetase system, p-hydroxyphenylglycine biosynthetic genes, an S-adenosylmethionine-dependent 3-amino-3-carboxypropyl transferase (Nat), and a cytochrome P450 . Gene disruption mutants of Nat, as well as an activation domain of the NRPS system, led to loss of nocardicin A formation . Several enzymes involved in antibiotic biosynthesis were heterologously overproduced, and biochemical characterization confirmed their proposed activities. J Antimicrob Chemother, 2004 Aug, 54(2), 529 - 33 Epub 2004 Jul 21. Development of a prescribing indicator for objective quantification of antibiotic usage in secondary care; Curtis C et al.; OBJECTIVES: To compare the recognized defined daily dose per 100 bed-days (DDD/100 bed-days) measure with the defined daily dose per finished consultant episode (DDD/FCE) in a group of hospitals with a variety of medicines management strategies . To compare antibiotic usage using the above indicators in hospitals with and without electronic prescribing systems . METHODS: Twelve hospitals were used in the study . Nine hospitals were selected and split into three cohorts (three high-scoring, three medium-scoring and three low-scoring) by their 2001 medicines management self-assessment scores (MMAS) . An additional cohort of three electronic prescribing hospitals was included for comparison . MMAS were compared to antibiotic management scores (AMS) developed from a questionnaire relating specifically to control of antibiotics . FCEs and occupied bed-days were obtained from published statistics and statistical analyses of the DDD/100 bed-days and DDD/FCE were carried out using SPSS . RESULTS: The DDD/100 bed-days varied from 81.33 to 189.37 whilst the DDD/FCE varied from 2.88 to 7.43 . The two indicators showed a high degree of correlation with r=0.74 . MMAS were from 9 to 22 (possible range 0-23) and the AMS from 2 to 13 (possible range 0-22) . The two scores showed a high degree of correlation with r=0.74 . No correlation was established between either indicator and either score . CONCLUSIONS: The WHO indicator for medicines utilization, DDD/100 bed-days, exhibited the same level of conformity as that exhibited from the use of the DDD/FCE indicating that the DDD/FCE is a useful additional indicator for identifying hospitals which require further study . The MMAS can be assumed to be an accurate guide to antibiotic medicines management controls . No relationship has been found between a high degree of medicines management control and the quantity of antibiotic prescribed. Cochrane Database Syst Rev . 2004;(3):CD004400. Granulocyte-Colony Stimulating Factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults; Cheng AC et al.; BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number . Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropaenia, but its role in the treatment of infection in non-neutropaenic hosts is less well defined . OBJECTIVES: We explored the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropaenic adults . SEARCH STRATEGY: We searched the following electronic databases in 2003 and updated the search in 2004: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004); MEDLINE (January 1966 to March Week 1, 2004); EMBASE (1998 to December 2003); online databases of clinical trials; and reference lists of articles . We also contacted study authors, manufacturers and distributors of G-CSF . SELECTION CRITERIA: We considered randomised controlled trials (RCTs) which included hospitalised adult patients with either community acquired pneumonia or hospital-acquired pneumonia . DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality . The primary outcome measure was 28 day mortality . Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction . An assessment of methodological quality was made for each study . MAIN RESULTS: Six studies with a total of 1984 people were identified . G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ dysfunction . However, the use of G-CSF was not associated with improved 28 day mortality (pooled OR 0.86; 95% CI: 0.56 to 1.31) . REVIEWERS' CONCLUSIONS: There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia . Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest. J Biomed Mater Res, 2004 Aug 15, 70B(2), 332 - 9 High release of antibiotic from a novel hydroxyapatite with bimodal pore size distribution; Hasegawa M et al.; We developed a novel hydroxyapatite (HA) cylinder (HA-A) and compared the slow release of antibiotic in vitro as well as osteoconduction of the material in vivo to a commercially produced porous hydroxyapatite cylinder (HA-B) . HA-A (4 x 4 mm) was synthesized by mixing HA powder, gelatin, and vegetable oil . The material had a bimodal pore size distribution, with intragranular (10 nm to 10 microm) and intergranular (100 microm) pores, and porosity of 40 vol %, while HA-B had pore sizes ranging from 50 to 300 microm and identical porosity . In vitro drug release was tested using antibiotics (isepamicin sulfate, vancomycin hydrochloride, and flomoxef sodium) soaked on the HA cylinders using a vacuum system . The mean adsorption efficiency was higher for HA-A (46%) than for HA-B (26%) and higher levels of antibiotic were released from HA-A . Of the antibiotics, ISP showed the longest release duration . Bone ingrowth into the pores was observed for both materials . Because the novel HA showed both the slower release of antibiotic (nanosize pores) and supported excellent osteoconduction (microsize pores), it could be useful for the treatment of osteomyelitis . Cell Tissue Bank, 2004, 5(1), 23 - 36 Application of a high-level peracetic acid disinfection protocol to re-process antibiotic disinfected skin allografts; Lomas RJ et al.; Skin allografts, derived from cadaveric donors, are widely used for the treatment of burns and ulcers . Prior to use in clinical situations, these allografts are disinfected using a cocktail of antibiotics and then cryopreserved . Unfortunately, this antibiotic disinfection procedure fails to decontaminate a significant proportion and these contaminated grafts can not be used clinically . We have investigated whether it is possible to apply a second, more potent disinfection procedure to these contaminated grafts and effectively to re-process them for clinical use . Cadaveric skin grafts, treated with antibiotics and cryopreserved, were thawed and a peracetic acid (PAA) disinfection protocol applied . The grafts were then preserved in a high concentration of glycerol or propylene glycol, and properties thought to be essential for successful clinical performance assessed . The cytotoxicity of the grafts was assessed using both extract and contact assays; damage to the skin collagen was assessed using a collagenase susceptibility assay and the capacity of the grafts to elicit an inflammatory response in vitro was assessed by quantifying the production of the pro-inflammatory cytokine TNF-alpha by human peripheral blood mononuclear phagocytes . PAA disinfection, in conjunction with either glycerol or propylene glycol preservation, did not render the grafts cytotoxic, pro-inflammatory, or increase their susceptibility to collagenase digestion . The rates of penetration of glycerol and propylene glycol into the re-processed skin were comparable to those of fresh skin . This study has demonstrated that PAA disinfection combined with immersion in high concentrations of either glycerol or propylene glycol was an effective method for re-processing contaminated skin allografts, and may justify their clinical use. J Oral Implantol, 2004, 30(3), 144 - 51 AICRG, Part III: The influence of antibiotic use on the survival of a new implant design; Morris HF et al.; PURPOSE: The American College of Surgeons guidelines suggest that complex oral surgery may benefit from prophylactic antibiotic coverage . The use of preoperative antibiotics, postoperative antibiotics, or both during implant placement is a widely accepted practice in the United States, whereas dentists in other countries rarely use antibiotics . PURPOSE: The purpose of this study was to determine if antibiotic coverage at the time of implant placement improves the survival of the Ankylos implant . METHODS: As part of a comprehensive, multicentered, multidisciplinary, prospective, independent, international clinical study, designed and coordinated in the United States by the Ankylos Implant Clinical Research Group (AICRG), the use of preoperative (several regimens) and postoperative antibiotics (yes/no) were carefully documented to assess their influence on improving survival . A total of 1500 Ankylos implants were placed and followed for a period of 3 to 5 years . The decision to use antibiotics and the regimen to be employed was made by the treating surgeon . Failure was defined as removal of the implant for any reason . All data were entered into a computerized database for analysis . RESULTS: The use of preoperative antibiotics produced no significant improvement (P = .21, Fisher's exact test) in survival compared with those placed without antibiotic coverage . There was no significant difference between the regimens defined as AHA-1990, AHA-1997, and Peterson's recommendations . CONCLUSIONS: The results of this study suggest that there was little or no advantage to providing antibiotic coverage when placing this implant . These findings also suggest that the use of antibiotics for implant placement may not be as beneficial as once believed . If validated by other studies, the elimination of this practice for routine implant placement would represent a small but significant step forward in the reduction of unnecessary antibiotic use. J Environ Qual, 2004 Jul-Aug, 33(4), 1331 - 42 Sorption of sulfonamide pharmaceutical antibiotics on whole soils and particle-size fractions; Thiele-Bruhn S et al.; Residues of pharmaceutical antibiotics are found in the environment, whose fate and effects are governed by sorption . Thus, the extent and mechanisms of the soil sorption of p-aminobenzoic acid and five sulfonamide antibiotics (sulfanilamide, sulfadimidine, sulfadiazine, sulfadimethoxine, and sulfapyridine) were investigated using topsoils of fertilized and unfertilized Chernozem and their organic-mineral particle-size fractions . Freundlich adsorption coefficients (K(f)) ranged from 0.5 to 6.5 . Adsorption increased with aromaticity and electronegativity of functional groups attached to the sulfonyl-phenylamine core . Adsorption to soil and particle-size fractions increased in the sequence: coarse silt < whole soil < medium silt < sand < clay < fine silt and was influenced by pH . Sorption nonlinearity (1/n </= 0.76) indicated specific interactions with functional groups of soil organic matter (SOM) . Phenolic and carboxylic groups, N-heterocyclic compounds, and lignin decomposition products were tentatively assigned as preferred binding sites using statistical analysis of pyrolysis-mass spectra and adsorption coefficients . Adsorption of sulfonamides to mineral soil colloids was weaker and resulted in a stronger desorption from clay-size fractions . Moreover, steric accessibility of organic-mineral complexes in clay-size fractions was significantly reduced . With a quantitative structure-property relationship (QSPR) model, combining the organic carbon concentration, the sulfonamides' chromatographic capacity factor (k'), and nondissociated species concentration (CF(a)), distribution coefficients (K(d)) were estimated with a cross-validated regression coefficient Q(2) = 0.71 . Modeling and molecular mechanics calculations of antibiotic-SOM complexes showed preferred site-specific sorption via hydrogen bonds and van der Waals interactions . Distinct chemical structural properties, such as aromaticity and van der Waals volumes, correlated with the sorption data. J Natl Med Assoc, 2004 Jul, 96(7), 945 - 7 Steroids and antibiotics for treatment of acute asthma exacerbations in African-American children; Rodrigues RG; BACKGROUND: There has been great debate surrounding the appropriate treatment regimens in children who present with acute asthma exacerbations secondary to upper respiratory tract infections . OBJECTIVE: To determine whether treatment with corticosteroids alone or in combination with antibiotics will decrease respiratory symptoms in children who develop asthma exacerbations secondary to upper respiratory tract infections . METHODS: A retrospective cohort control study involving 86 African-American children, ages 5-16, with mild intermittent asthma . The patients were treated with an albuterol inhaler (control group), inhaler plus five days of Prednisone; or inhaler, Prednisone, and 10 days of Amoxicillin . All patients were assessed regarding peak flows, albuterol inhaler usage, and symptomatology . RESULTS: On follow up five- to seven days after presentation, the corticosteroids group demonstrated a marked improvement in peak flows (88% versus 77%) and a significantly lower albuterol inhaler usage rate (2.2 versus 3.7 times a day) relative to the control group . The corticosteroids plus antibiotics group demonstrated peak flows (86% versus 88%) and inhaler usage (2.4 versus 2.2) nearly identical to corticosteroids alone, but the severity of underlying respiratory symptoms was significantly less . CONCLUSION: A five-day course of oral corticosteroids will significantly improve lung function and lessen severity of asthma symptoms . The addition of antibiotics to the treatment regimen has no additive effect on the reactive airway symptoms. Clin Exp Allergy, 2004 Jul, 34(7), 1011 - 6 Antibiotic use in the first year of life and asthma in early childhood; Celedon JC et al.; BACKGROUND: An association between antibiotic use in early life and asthma in childhood has been reported in five retrospective studies and one longitudinal study . OBJECTIVE: To examine the relation between the use of oral antibiotics in the first year of life and asthma in early childhood . METHODS: Longitudinal follow-up of 4408 children enrolled in a health maintenance organization (HMO) from birth to the age of 5 years . RESULTS: After adjusting for sex and illnesses of the lower respiratory tract (LRIs), we found a significant association between antibiotic use in the first year of life and asthma between the ages of 1 and 2 years (odds ratio (OR) for 1-2 vs . no courses of antibiotics=1.9, 95% confidence interval (CI)=1.3-2.7; OR for 3-4 vs . no courses of antibiotics=1.6, 95% CI=1.1-2.4; OR for at least 5 vs . no courses of antibiotics=2.1, 95% CI=1.5-3.2) . After adjustment for sex and LRIs in the first year of life, there was no significant association between antibiotic use in the first year of life and asthma that was initially diagnosed between the ages of 2 and 5 years and that persisted up to the age of 5 years (OR for 1-2 vs . no courses of antibiotics=1.1, 95% CI=0.8-1.4; OR for 3-4 vs . no courses of antibiotics=1.3, 95% CI=0.9-1.8; OR for at least 5 vs . no courses of antibiotics=1.0, 95% CI=0.7-1.4) . Conclusions Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma in childhood but rather suggest that frequent antibiotic use in early life is more common among asthmatic children. Bioorg Med Chem, 2004 Aug 1, 12(15), 4075 - 80 Acid-base versus structural properties of an aminoglycoside antibiotic--sisomicin: NMR and potentiometric approach; Krezel A et al.; Aminoglycoside antibiotics constitute a class of the drugs of high interest, whose therapeutic action is based upon the electrostatic interaction with the variety of RNA molecules . The positive charge of these drugs molecules, located at their amino functions, has a prevailing influence on this process . The potentiometry and (1)H NMR spectroscopy are applied hereby to achieve the characteristics of the acid-base properties of particular protonating groups . We found that the p {Formula: see text} values of deprotonation processes cover a wide values range 6-9.8 . The correlation spectra of sisomicin, both COSY and TOCSY, allowed attributing unambiguously individual signals to the corresponding protons . These spectra involve a lot of the cross-peaks originating from the B and C rings protons, while the analogous signals originating from A rings protons are less numerous . Molecular modeling provided that the methylated amino group of A ring is located too far from the protonated functions of the remaining rings to affect their pK values . The phenomena observed herein are discussed in line of strength of the analogous processes observed for other aminoglycosides . As the result, four types of amino groups consisted within these antibiotics are distinguished. Peptides, 2004 Jul, 25(7), 1079 - 84 Parabutoporin--an antibiotic peptide from scorpion venom--can both induce activation and inhibition of granulocyte cell functions; Willems J et al.; Parabutoporin (PP) affects motility and NADPH oxidase activity in normal human polymorphonuclear neutrophils and in granulocytic HL-60 cells . These PP-induced interactions utilize a Rac activation pathway . PP induces chemotaxis of neutrophils and HL-60 cells via a pertussis toxin-sensitive way, thus using trimeric G-proteins . The enhanced chemotaxis is also apparent in undifferentiated HL-60 cells which lack functional formyl peptide receptors . On the other hand, PP strongly reduces the superoxide production by the NADPH oxidase complex after either PMA or fMLP activation of granulocytes . These combined results strongly suggest a direct activation of G-proteins and subsequent Rac activation as the basis for the observed effects . The unexpected inhibitory effect of PP, despite Rac activation, on superoxide production in granulocytes is explained by the direct interaction of membrane localized PP which prevents the formation of a functional NADPH oxidase complex. Dent Traumatol, 2004 Aug, 20(4), 203 - 11 Healing of 400 intra-alveolar root fractures . 2 . Effect of treatment factors such as treatment delay, repositioning, splinting type and period and antibiotics; Andreasen JO et al.; This is the second part of a retrospective study of 400 root-fractured permanent incisors . In this article, the effect of various treatment procedures is analyzed . Treatment delay, i.e . treatment later than 24 h after injury, did not change the root fracture healing pattern, healing with hard tissue between fragments (HH1), interposition of bone and/or periodontal ligament (PDL) or pulp necrosis (NEC) . When initial displacement did not exceed 1 mm, optimal repositioning appeared to significantly enhance both the likelihood of pulpal healing and hard tissue repair (HH1) . Significant differences in healing were found among the different splinting techniques . The lowest frequency of healing was found with cap splints and the highest with fiberglass or Kevlar splints . The latter splinting procedure showed almost the same healing result as non-splinting . Comparison between non-splinting and splinting for non-displaced teeth was found to reveal no benefit from splinting . With respect to root fractures with displacement, too few cases were available for analysis . No beneficial effect of splinting periods greater than 4 weeks could be demonstrated . The administration of antibiotics had the paradoxical effect of promoting both HH1 and NEC . No explanation could be found . It was concluded that, optimal repositioning seems to favor healing . Furthermore, the chosen splinting method appears to be related to healing of root fractures, with a preference to pulp healing and healing fusion of fragments to a certain flexibility of the splint and possibly also non-traumatogenic splint application . Splinting for more than 4 weeks was not found to influence the healing pattern . A certain treatment delay (a few days) appears not to result in inferior healing . The role of antibiotics upon fracture healing is questionable . Copyright Blackwell Munksgaard, 2004. Eur J Prosthodont Restor Dent, 2004 Jun, 12(2), 63 - 9 Systemic antibiotics in the management of chronic periodontitis; Preshaw PM; Multiple research studies have investigated the use of systemic antibiotics as adjunctive treatments in the management of chronic periodontitis . However, the great heterogeneity of study designs and variable outcomes that have been reported have led to confusion among the profession as to whether or not there is any clinical benefit of using systemic antibiotics . In this review, the potential advantages and disadvantages of using systemic antibiotics are considered together with outcomes from published clinical studies . Few published studies are of adequate quality to be considered in systematic reviews, and the outcomes are very varied . Drawing definitive conclusions is difficult, but given the lack of reliable data available, systemic antibiotics cannot be indicated as adjuncts in the treatment of chronic periodontitis. Immunol Allergy Clin North Am, 2004 Aug, 24(3), 533 - 43, viii Multiple antibiotic allergy syndrome; Macy E; Allergists/immunologists are commonly referred patients with histories of multiple antibiotic allergies and must determine what antibiotics they can safely use . This review covers articles published through September 2003 . The history and definition of multiple antibiotic allergy syndrome are discussed . The clinical and laboratory evidence suggesting that certain individuals make allergic antibody to unrelated antibiotics is explored . A framework for dealing with this potentially vexing problem on a clinical level is developed . Areas that require additional research and development are outlined. Prim Dent Care, 2004 Jul, 11(3), 77 - 80 An audit of antibiotic prescribing by vocational dental practitioners; Palmer NO et al.; OBJECTIVES: To investigate antibiotic prescribing of a group of vocational dental practitioners (VDPs) and assess the implications for postgraduate education . DESIGN: A prospective audit was carried out by VDPs in general dental practice in 2003 . RESULTS: A total of seven vocational training schemes comprising 64 VDPs took part . Most showed some awareness of the indications for therapeutic prescribing but the prescribing patterns of a number were influenced by the pressure of time and workload and difficulty in making a definitive diagnosis . There were wide variations in the therapeutic antibiotic regimens used, with most not conforming to the guidelines available . The majority of VDPs showed a good understanding of the requirement for prescribing prophylactic antibiotics for patients with a cardiac defect but a number also prescribed when there were no medical indications to do so . CONCLUSIONS: From this audit it is clear that, on occasions, the prescribing of antibiotics by VDPs was not consistent with current knowledge and within the guidelines available . This calls into question the efficacy of present undergraduate teaching or the retention of knowledge . The results suggest that formal education on antibiotic prescribing in general dental practice should take place during the VT year. Biophys J, 2004 Jul, 87(1), 58 - 64 Microscopic Mechanism of Antibiotics Translocation through a Porin; Ceccarelli M et al.; OmpF from the outer membrane of Escherichia coli is a general porin considered to be the main pathway for beta-lactam antibiotics . The availability of a high-resolution crystal structure of OmpF and new experimental techniques at the single-molecule level have opened the way to the investigation of the microscopic mechanisms that allow the passage of antibiotics through bacterial pores . We applied molecular dynamics simulations to investigate the translocation process of ampicillin (Amp) through OmpF . Using a recent algorithm capable of accelerating molecular dynamics simulations we have been able to obtain a reaction path for the translocation of Amp through OmpF . The mechanism of passage depends both on the internal degrees of freedom of Amp and on interactions of Amp with OmpF . Understanding this mechanism would help us design more efficient antibiotics and shed light on nature's way of devising channels able to enhance the transport of molecules through membranes. Biochim Biophys Acta, 2004 Jul 1, 1664(1), 31 - 7 Surface behaviour and peptide-lipid interactions of the antibiotic peptides, Maculatin and Citropin; Ambroggio EE et al.; Surface behaviour of Maculatin 1.1 and Citropin 1.1 antibiotic peptides have been studied using the Langmuir monolayer technique in order to understand the peptide-membrane interaction proposed as critical for cellular lysis . Both peptides have a spontaneous adsorption at the air-water interface, reaching surface potentials similar to those obtained by direct spreading . Collapse pressures (Pi(c), stability to lateral compression), molecular areas at maximal packing and surface potentials (DeltaV) obtained from compression isotherms of both pure peptide monolayers are characteristic of peptides adopting mainly alpha-helical structure at the interface . The stability of Maculatin monolayers depended on the subphase and increased when pH was raised . In an alkaline environment, Maculatin exhibits a molecular reorganization showing a reproducible discontinuity in the Pi-A compression isotherm . Both peptides in lipid films with the zwitterionic palmitoyl-oleoyl-phosphatidylcholine (POPC) showed an immiscible behaviour at all lipid-peptide proportions studied . By contrast, in films with the anionic palmitoyl-oleoyl-phosphatidylglycerol (POPG), the peptides showed miscible behaviour when the peptides represented less than 50% of total surface area . Additional penetration experiments also demonstrated that both peptides better interact with POPG compared with POPC monolayers . This lipid preference is discussed as a possible explanation of their antibiotic properties. Tidsskr Nor Laegeforen, 2004 Jun 17, 124(12), 1620 - 3 {The use of paracetamol and antibiotics among preschool children}; Lagerlov P et al.; BACKGROUND: Sales of paracetamol in paediatric formulations are increasing and antibiotics are frequently prescribed to children . Our aim was to study the use of paracetamol and antibiotics in different age groups among preschool children . MATERIAL AND METHODS: Parents of 1312 children (99% response rate) visiting public health centres were asked to state how often their child had been sick, used paracetamol, seen a doctor, or used antibiotics during the previous three months . If the child had used antibiotics, parents were asked to give the reason for treatment, the name of the drug used, and the duration of treatment . RESULTS: 71% of the children had been sick, 46% had received paracetamol, 36% had seen a doctor, and 12% had used antibiotics . The highest frequency of illness and paracetamol use was seen among children one to two years of age . Otitis was the main reason for using antibiotics in children of one to four years of age, and the duration of treatment was often longer than recommended . INTERPRETATION: Use of paracetamol is widespread among preschool children . Parents going back to work after maternity leave and more frequent fever resulting from exposure to infections may contribute to an increased use of paracetamol . Restrictive use of antibiotics for otitis and shorter treatment duration continue to be emphasised. Org Biomol Chem, 2004 Jul 7, 2(13), 1872 - 8 Epub 2004 Jun 15. NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin; Ball LJ et al.; Daptomycin is an acidic lipopeptide antibiotic, whose three-dimensional structure and mechanism of action is currently unknown . Recently daptomycin, trade name Cubicin, was approved as a drug for the treatment of skin-related infections (M . Larkin Lancet, 2003, 3, 677) and became the first antibiotic of its class to be used in the clinic (A . Raja et al., Nature Rev . Drug Discov., 2003, 2, 943-944) . We have carried out a systematic high field NMR study of daptomycin and its binding to calcium ions which is essential for antibiotic activity . In this first report, we demonstrate the sequence-specific resonance assignment of daptomycin under resolved NMR measurement conditions . In addition to this, we have determined the 3D structure of apo-daptomycin and demonstrated a 1 : 1 stoichiometry on the binding to calcium ions . We have also demonstrated that the binding of calcium ions does not result in major conformational changes, but does induce aggregation . This may be an important factor in the mode of action of daptomycin. J Am Board Fam Pract, 2004 May-Jun, 17(3), 196 - 200 Antibiotics for upper respiratory tract infections in ambulatory practice in the United States, 1997-1999: does physician specialty matter? Rutschmann OT, Domino ME. BACKGROUND: The dangers of overuse of antibiotics for upper respiratory infections (URIs) has been widely recognized, but the rate of change in prescribing patterns in recent years is unknown . METHODS: Data on the use of antibiotics for URIs was extracted from the 1997 to 1999 National Ambulatory Medical Care Survey (a national multistage probability sample survey of patients' office visits to office-based physicians) . Adult patients (>/=18 years) with a primary diagnosis of URI (bronchitis, common colds, and other acute upper respiratory infections) were included . The decision to prescribe antibiotics was modeled as a function of patient, physician, and practice characteristics using logistic regression . RESULTS: The rate of antibiotic prescription for URIs decreased from 52.1% in 1997 to 41.5% in 1999 . In a multivariate logistic regression model, treatment by general internal medicine physicians {odds ratio (OR), 0.37; 95% confidence interval (CI), 0.18 to 0.76} was associated with lower prescription rates . Of patients visiting general internal medicine physicians for URIs, 36.2% received antibiotics compared with 42.9% of those seeing a general/family medicine physician . Patients treated by their primary care physicians had a higher risk of receiving antibiotics (OR, 1.70; 95% CI, 1.08 to 2.68) . CONCLUSIONS: Despite a downward trend in antibiotic prescribing over the years, overprescription of antibiotics for upper respiratory infections persists . General internal medicine physicians are less likely than general/family physicians to prescribe antibiotics, but this gap seems to be narrowing . Specific interventions must be designed to address these disparities. Nurs Stand, 2004 Jun 16-22, 18(40), 38 - 42 Bacterial infections: antibiotics and decontamination; Gould D; Infectious disease is caused by bacteria, viruses, fungi, protozoa and micro-organisms including the mycoplasmas, rickettsiae and chlamydiae . Most of the infections commonly encountered in the UK are caused either by bacteria or viruses . This article describes bacterial structure and function to explain how antibiotics work and the processes of decontamination such as cleaning, disinfection and sterilisation, which are important in infection control. Water Res, 2004 Jul, 38(12), 2874 - 90 Potentiometric determination of acid dissociation constants (pKa) for human and veterinary antibiotics; Qiang Z et al.; This work determined the acid dissociation constants (pKa) of 26 common human and veterinary antibiotics by potentiometric titration . Selected antibiotics consisted of sulfonamides, macrolides, tetracyclines, fluoroquinolones, and other miscellaneous antibiotics . After validation of analysis methods using phosphoric acid as a model compound, a second-derivative (delta2pH/deltaV2) method was primarily applied to determining pKa's from titration curves for most antibiotics due to its convenience and accuracy . For tetracyclines, however, a least-square non-linear regression method was developed to determine their pKa's because the second-derivative method cannot well distinguish the pKa,2 and pKa,3 of tetracyclines . Results indicate that the pKa values are approximately 2 and 5-7.5 for sulfonamides; 7.5-9 for macrolides; 3-4, 7-8 and 9-10 for tetracyclines; 3-4, 6, 7.5-9 and 10-11 for fluoroquinolones; while compound-specific for other miscellaneous antibiotics . The moieties corresponding to specific pKa's were identified based on chemical structures of antibiotics . In addition, the pKa's available in literature determined by various techniques are compiled in comparison with the values of this work . These results are expected to essentially facilitate the research on occurrence, fate and effects, analysis methods development, and control of antibiotics in various treatment operations. Biophys Chem, 2004 Jul 1, 110(1-2), 101 - 17 Effect of the phospholipid head group in antibiotic-phospholipid association at water-air interface; Gambinossi F et al.; We studied the interactions of tetracycline antibiotics, TCs, with phospholipid monolayers with the two-fold aim of elucidating the mechanism of action of TCs and to provide a first step for the realization of bio-mimetic sensor for such drugs by means of the Langmuir-Blodgett technique . Preliminary surface tension studies demonstrated that surface activity of tetracycline is moderate and dependent on the pH of the subphase . We selected three phospholipids having hydrophobic chains of the same length but differing in the polar head structures, i.e . dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, and dipalmitoylphosphatidic acid . Surface pressure- and surface potential- area isotherms were employed to investigate the behavior of the phospholipid monolayers at the water-air interface when tetracycline was added to the aqueous subphase . Analysis of the results indicated that the electrostatic interaction is the driving force for migration of tetracycline towards the interface where localized adsorption to the head groups occurs . Nevertheless, such interactions appear to be insufficient to promote penetration of tetracycline through the hydrophobic layer. Int Immunopharmacol, 2004 Aug, 4(8), 1067 - 73 Commonly used antibiotics induce expression of Hsp 27 and Hsp 60 and protect human lymphocytes from apoptosis; Romano CC et al.; Heat shock proteins (Hsps) are abundant molecular chaperones participating in the cytoprotection . The kinetics of synthesis of Hsps closely correlates with the kinetics of development of resistance to cell death . In this study, we analysed the probable involvement of Hsp 27 and Hsp 60 in the protection of cells undergoing apoptosis . Human lymphocytes cultured in the presence of ampicillin or ceftriaxone produced Hsp 60 and Hsp 27, estimated by immunoblotting in a time-dependent manner and the increased levels of Hsp 60 and Hsp 27 correlated with enhanced resistance of the lymphocytes to apoptosis, as determined by flow cytometry . Cultures treated with ampicillin or ceftriaxone also exhibited smaller numbers of apoptotic cells than untreated cultures when exposed to the apoptosis-inducing agent staurosporine (1 mM) . In contrast, cloramphenicol induced the production of only small amounts of Hsp 60, and no resistance apoptosis . Further studies are needed to clarify the potential role of Hsp 27 and Hsp 60 in the resistance of human cells to apoptosis and the effects of antibiotics on this phenomenon. Biochem Biophys Res Commun, 2004 Jul 23, 320(2), 557 - 62 The sterol-binding antibiotic nystatin differentially modulates ligand binding of the bovine hippocampal serotonin1A receptor; Pucadyil TJ et al.; We have monitored the ligand binding of the bovine hippocampal 5-HT1A receptor following treatment with the sterol-binding antifungal antibiotic nystatin . Nystatin considerably inhibits the specific binding of the antagonist to 5-HT1A receptors in a concentration-dependent manner . However, the specific agonist binding does not show significant changes . Fluorescence polarization measurements of membrane probes incorporated at different locations in the membrane revealed a substantial decrease in the membrane order in the interior of the bilayer . Experiments with cholesterol-depleted membranes indicate that the action of nystatin is mediated through membrane cholesterol . These results represent the first report on the effect of a cholesterol-perturbing agent on the ligand-binding activity of this important neurotransmitter receptor. Prog Urol, 2004 Apr, 14(2), 154 - 9 {Prophylactic antibiotics in urological surgery: compliance of prescriptions in Franche-Comté with national guidelines}; Talon I et al.; STUDY OBJECTIVE: To evaluate prophylactic antibiotic practices in urological surgery in Franche-Comte . MATERIAL AND METHODS: Six urological surgery teams participated in data collection . Practices were evaluated in comparison with national guidelines by means of five questions: Did the surgical operation justify prophylactic antibiotics and was this treatment administered? Was the antibiotic selected that recommended by national guidelines? Was the total duration appropriate? Was the time of the first injection appropriate? Was the dosage appropriate? The Societe Francaise d'Anesthesie et de Reanimation (SFAR) guidelines, revised in 1999, constituted the reference . RESULTS: Of the 213 operations included in the study, 134 corresponded to Altemeier class 1 and 2 operations for which the SFAR has issued guidelines . The overall compliance rate was 22.6% . Among the 56 patients who did not receive the recommended molecule, 45 received a molecule with a broader spectrum of activity than that of the recommended molecule . The duration of prophylactic antibiotics was longer for 10 of the 11 patients in whom the duration of prophylaxis did not comply with guidelines . Finally, for more than one third of operations, the time of injection of the first dose was not optimal . CONCLUSION: This study demonstrated the high frequency of non-compliance with prophylactic antibiotic prescription guidelines in urological surgery in Franche-Comte . These guidelines must be reinforced and applied to ensure the efficacy of prophylactic antibiotics and to avoid the emergence of resistant strains. Rev Mal Respir, 2004 Apr, 21(2 Pt 1), 381 - 9 {ANTEAB: a study of early antibiotic therapy in intensive care management of acute exacerbations of chronic obstructive lung disease}; Fartoukh M et al.; INTRODUCTION: Intensive Care Unit (ICU) admission for acute exacerbation of chronic obstructive lung disease (COLD) is a major cause of morbidity and mortality in such patients . Although bacterial and/or viral infections are considered as the major precipitating factor, the antibiotic strategy in this setting is unclear . The potential benefit of routine antibiotic therapy in the absence of evidence of overt infection remains controversial, and has not been adequately studied in patients admitted to the ICU . To assess the benefit (or lack thereof) of routine early systemic antibiotic therapy in patients with COLD admitted to the ICU . METHODS: This is a multicenter, randomized, double-blind controlled trial, comparing amoxicillin-clavulanic acid administered for 7 days to a placebo . Patients included are those with documented or suspected COLD, exclusive of other bronchial or lung disease, and admitted for acute exacerbation, in the absence of overt sepsis or broncho-pneumonia, and having no other organ failure . Patients recently hospitalized, having received antibiotics for > 24 h, or on long-term steroids will not be included . Co-interventions (bronchodilators, steroids) are controlled for . Patients will be administered the antibiotic or placebo within 24 hours of admission . EXPECTED RESULTS: A 20% reduction of the duration of clinical symptoms of exacerbation is expected . To this end, 520 patients are planned to be included in 15 centers in a 2-year period . Secondary end-points are the incidence of documented infection (lower respiratory tract or other sites), antibiotic use, the proportion of patients having infection with resistant bacteria, the incidence of endotracheal intubation, the duration of stay and mortality in the ICU and the hospital. J Trauma, 2004 Jun, 56(6), 1247 - 52 Two-stage revision hip arthroplasty for infection with a custom-made, antibiotic-loaded, cement prosthesis as an interim spacer; Hsieh PH et al.; BACKGROUND: Two-stage reconstruction is a well-recognized treatment for deep infection of hip joint implants . The purpose of the study was to report the results of our treatment using a standardized protocol . METHODS: Forty-two consecutive patients with deep infection of the hip prosthesis were treated according to a prospective, two-stage resection/reimplantation protocol . Between stages, a custom-made, antibiotic-loaded, cement prosthesis was implanted as an interim spacer . RESULTS: Infection was eradicated in 41 patients after the first-stage operation . Thirty-six patients remained with the ability to walk with the interim cement pros-thesis . For 40 patients who underwent reimplantation, recurrence of infection was observed in only 1 patient at an average of 55.2 months' follow-up . CONCLUSION: We have found that our two-stage treatment protocol is a reliable approach for the management of infected hip prostheses . It is effective for eradicating infection and for providing a mobile and functional joint through the treatment course. Mikrobiol Z, 2004 Mar-Apr, 66(2), 69 - 73 {Sensitivity of Streptomyces globisporus 3-1--a highly active producer of landomycin E to its own and the other polyketide antibiotics}; Tymchyk OV et al.; The strain Streptomyces globisporus 3-1--a highly active producer of a new anticarcinogenic antibiotic landomycin E from the group of angucyclins has been studied for its resistance to its own and known polyketide antibiotics--tetracycline, oleandomycin and doxorubicine as well as to aminoglycoside antibiotic streptomycin . The survival of mycelium of the strain 3-1 was established to depend on antibiotics concentration . Four equal resistances of streptomycete to antibiotics within the concentration of 5-30 micrograms/ml have been shown . The survival of the strain 3-1 mycelium fragments at 5 micrograms/ml of antibiotic is for tetracycline--1.8, for olcandomycin--0.7; doxorubicin and landomycin E--(-0.7) and streptomycin--(-4.6) l g% . As to their intensity of the lethal effect on the strain 3.1 antibiotics show the following descending succession: streptomycin, landomycin E, doxorubicin, olcandomycin and tetracyclin . High sensitivity of the strain 3-1 to the lethal effect of its own antibiotic may be explained by high permeability of mycelium fragments to landomycin E as compared to the intact mycelium. Eur J Biochem, 2004 Jul, 271(13), 2682 - 90 Role of K22 and R120 in the covalent binding of the antibiotic fosfomycin and the substrate-induced conformational change in UDP-N-acetylglucosamine enolpyruvyl transferase; Thomas AM et al.; UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), catalyzes the first step in the biosynthesis of peptidoglycan, involving the transfer of the intact enolpyruvyl moiety from phosphoenolpyruvate to the 3'-hydroxyl group of UDP-N-acetylglucosamine (UDPNAG) . The enzyme is irreversibly inhibited by the antibiotic fosfomycin . The inactivation is caused by alkylation of a highly conserved cysteine residue (C115) that participates in the binding of phosphoenolpyruvate . The three-dimensional structure of the enzyme suggests that two residues may play a decisive role in fosfomycin binding: K22 and R120 . To investigate the role of these residues, we have generated the K22V, K22E, K22R and R120K single mutant proteins as well as the K22V/R120K and K22V/R120V double mutant proteins . We demonstrated that the K22R mutant protein behaves similarly to wild-type enzyme, whereas the K22E mutant protein failed to form the covalent adduct . On the other hand, the K22V mutant protein requires the presence of UDPNAG for the formation of the adduct indicating that UDPNAG plays a crucial role in the organization of productive interactions in the active site . This model receives strong support from heat capacity changes observed for the K22V/R120K and R120K mutant proteins: in both mutant proteins, the heat capacity changes are markedly reduced indicating that their ability to form a closed protein conformation is impeded due to the R120K exchange. J Antimicrob Chemother, 2004 Aug, 54(2), 295 - 8 Epub 2004 Jun 16. The expanding role of the antibiotic pharmacist; Weller TM et al.; Widespread inappropriate prescribing of antibiotics in UK hospitals has led to the introduction of specialist antibiotic pharmacists . Their role is to monitor antibiotic use, advise clinicians, educate all grades of healthcare workers and help to develop policy . Antibiotic pharmacists have been shown to be effective in many situations . As these practitioners become more accomplished it will be possible to expand their role to include direct intervention in patient treatment . Simple measures, such as modification of intravenous treatment to oral and automatic stop orders, could greatly enhance patient care. Mol Cell, 2004 Jun 18, 14(6), 753 - 62 Molecular mechanism of transcription inhibition by Peptide antibiotic microcin j25; Adelman K et al.; 21 amino acid peptide Microcin J25 (MccJ25) inhibits transcription by bacterial RNA polymerase (RNAP) . MccJ25-resistance mutations cluster in the RNAP secondary channel through which incoming NTP substrates are thought to reach the catalytic center and the 3' end of the nascent RNA is likely to thread in backtracked transcription complexes . The secondary channel also accepts transcript cleavage factors GreA and GreB . Here, we demonstrate that MccJ25 inhibits GreA/GreB-dependent transcript cleavage, impedes formation of backtracked complexes, and can be crosslinked to the 3'-end of the nascent RNA in elongation complexes . These results place the MccJ25 binding site within the secondary channel . Moreover, single-molecule assays reveal that MccJ25 binding to a transcribing RNAP temporarily stops transcript elongation but has no effect on the elongation velocity between pauses . Kinetic analysis of single-molecule data allows us to put forward a model of transcription inhibition by MccJ25 that envisions the complete occlusion of the secondary channel by bound inhibitor. Intensive Care Med, 2004 Jul, 30(7), 1327 - 33 Epub 2004 Jun 09. Efficacy of adequate early antibiotic therapy in ventilator-associated pneumonia: influence of disease severity; Clec'h C et al.; OBJECTIVE: To test the hypothesis that the outcome of patients with ventilator-associated pneumonia (VAP) depends on both their baseline severity at VAP onset and the adequacy of empirical antibiotic therapy . DESIGN AND SETTING: Prospective clinical study in six intensive care units in Paris, France . PATIENTS . One hundred and forty-two patients with VAP after >/= 48 h of mechanical ventilation . MEASUREMENTS AND RESULTS: Patients were compared according to whether adequate antibiotics were started when VAP was first suspected (D0) . At day 0, the rate of adequate antibiotic therapy was 44.4% and rose to 92% at day 2 . Outcomes were recorded at the ICU and hospital discharge . Overall, no significant mortality difference was found with and without adequate early antibiotics . When patients were also classified based on the initial Logistic Organ Dysfunction score (LOD), mortality was significantly higher with inadequate early antibiotic therapy in the groups with LOD </= 4 (ICU mortality: 37% vs 7%, P=0.006; hospital mortality: 44% vs 15%, P=0.01) . A multivariate logistic regression confirmed that inadequate antibiotic therapy increased mortality in patients with LOD </= 4 after adjustment on other prognostic factors . CONCLUSIONS: Inadequate empirical treatment seemed to be associated with a poor prognosis only in patients with LOD </= 4 . These results need to be confirmed by further studies before any reappraisal of current guidelines for empirical antibiotic therapy of VAP can be envisaged. Arch Intern Med, 2004 Jun 14, 164(11), 1206 - 12 Improving the process of antibiotic therapy in daily practice: interventions to optimize timing, dosage adjustment to renal function, and switch therapy; Vogtlander NP et al.; BACKGROUND: Timely administration of the first dose, dosage adjustment to renal function, switch from intravenous to oral administration, and streamlining are important aspects of rational antibiotic prescription . The goals of this study were to investigate all of these variables, compare them with predefined quality standards, and implement improvement with specific interventions . METHODS: At the departments of internal medicine, surgery, and neurology and the emergency department of a tertiary referral university medical center, all consecutive patients receiving therapeutic antibiotics were enrolled . Dosages, timing of first doses, dosing intervals, administration routes, and adjustment of the chosen drug to clinical data were investigated . After the preintervention period, barriers to change were identified, followed by specific interventions and a postintervention measurement . RESULTS: In the preintervention and postintervention periods, 247 and 250 patients were enrolled, receiving 563 and 598 antibiotic prescriptions, respectively . The mean time from the order to first dose at the wards improved from 2.7 to 1.7 hours in potentially severe cases (P =.003) . Dosage adjustment to renal function remained unchanged at 45% vs 52% (P =.09) of cases where necessary . Switching of therapy from intravenous to oral improved from 46% to 62% (P =.03) and was performed a mean of 1.6 days earlier (P =.002) . Streamlining was performed correctly in most cases, and thus no interventions were necessary . CONCLUSIONS: Timing of antibiotic therapy and switch therapy may be improved with a combination of interventions . To improve poor adjustment of dosing to renal function, other strategies are needed . In our setting, streamlining was already correct in most cases. Adv Drug Deliv Rev, 2004 Jun 23, 56(10), 1481 - 96 Issues and challenges in developing long-acting veterinary antibiotic formulations; Sun Y et al.; Antibiotics are an important class of therapeutic agents, which are used for the treatment of bacterial infectious diseases in a variety of animal species . Antibiotic therapy varies from treatment period to administration routes, depending on the animal species or the type of the disease being treated . Despite the fact that there are a wide variety of commercially available antibiotics, difficulties and problems associated with the administration of antibiotics to animals still exist . Thus, there is a great need and tremendous opportunity to develop long-acting antibiotic formulations for veterinary applications . In this review article, common approaches used to develop long-acting antibiotic formulations are summarized . The challenges and issues related to the development of these long-acting formulations are also discussed. J Arthroplasty, 2004 Jun, 19(4 Suppl 1), 73 - 7 Prophylactic use of antibiotic bone cement: an emerging standard--in opposition; Hanssen AD; Antibiotic-loaded bone cement (ABLC) is an effective delivery method of local antibiotics . ABLC for treatment should be high dose (>3.6 g per 40 g cement) for beads or spacers and 1 to 2 g antibiotic per 40 g cement for prosthesis fixation . Multiple antibiotics are required for treatment, with antibiotics being individualized according to culture susceptibilities . This approach requires hand mixing because there are no commercial high-dose products . ABLC should be low dose (< or =1 g per 40 g cement) for prophylaxis purposes . Concerns with toxicity and cement mechanical properties are inconsequential with low-dose ABLC . Available clinical evidence supports low-dose ABLC for prophylaxis in revisions and high-risk primary joints, but concerns of emerging drug-resistant organisms probably outweigh routine use of low-dose ABLC in all uncomplicated primary arthroplasties. J Arthroplasty, 2004 Jun, 19(4 Suppl 1), 69 - 72 Prophylactic use of antibiotic bone cement: an emerging standard--in the affirmative; Bourne RB; Deep infection is a devastating complication following total joint arthroplasty . Preclinical testing; randomized; clinical trials; national joint replacement data; and our experience indicate that the use of antibiotic-impregnated bone cement is a potentially effective strategy in reducing the risk of deep infection following both primary and revision total joint arthroplasty . Allergic reactions, bacterial resistance, and cost represent barriers to the widespread use of antibiotic bone cement. Rev Prat, 2003 Sep 30, 53(14), 1566 - 71 {Antibiotic therapy in the elderly}; Veyssier P; The management of antibiotherapy in elderly patients is a unique and challenging problem . Old patients often suffer more serious complications of infection, more serious adverse events and drug interaction with drug therapy . The choice of antibiotherapy must also take into account the evolution of bacterial ecology . About one third of persons older than 80 and a higher proportion of elderly disabled patients reside in long term care facilities . And now, bacterial flora in institutions remains intermediate between that of community acquired infections and the more antibiotic resistant hospital flora. Health Econ, 2004 Jun, 13(6), 585 - 95 Resistance-induced antibiotic substitution; Howard DH; In many cases, physicians prescribe antibiotics without knowing whether an individual patient is infected with a susceptible or resistant pathogen . As the proportion of resistant organisms in a community increases, physicians substitute away from older-inexpensive drugs to newer, more expensive agents as first line therapy . This paper explores the implications of resistance-induced antibiotic substitution for epidemiological models to predict future resistance levels, efforts to measure the health care costs associated with resistance, and policies to improve physicians' antibiotic prescribing decisions . The extent of resistance-induced substitution in outpatient settings is documented using a data set consisting of observations on initial physician office visits for otitis media in the US controlling for new product introductions and price increases, per prescription antibiotic spending increased by 22% between 1980 and 1996, corresponding to a steep increase in resistance levels over the same period . Arch Pediatr Adolesc Med, 2004 Jun, 158(6), 577 - 83 A randomized controlled trial to change antibiotic prescribing patterns in a community; Doyne EO et al.; BACKGROUND: Excessive and inappropriate use of antibiotics has been identified as a leading cause of the emergence of multiply resistant strains of pneumococci . OBJECTIVE: To examine the effects of academic detailing and a parental education program on community pediatricians' prescription of antibiotics for young children . METHODS: Physician leaders in study practices prepared educational modules and presented the modules to their practices . The control groups received only practice-specific report cards . Using a time-series analysis, we collected data on office visits and antibiotic prescriptions filled between May 1, 2000, and April 30, 2001 (baseline period), and between May 1, 2001, and April 30, 2002 (intervention period) . Antibiotic prescription rate was defined as the ratio of antibiotic prescriptions filled to the number of office visits . RESULTS: The antibiotic prescription rate decreased to 0.82 (95% confidence interval, 0.71-0.95) of the baseline rate for the study group (6 practices) and to 0.86 (95% confidence interval, 0.77-0.95) of the baseline for the control group (5 practices) . Similar patterns for antibiotic prescription rates were seen for study and control groups both before and after the intervention . Wide variations in prescription rates were observed among the practices, but, in general, the control practices had lower antibiotic prescribing rates during both the baseline and the intervention periods . Use of amoxicillin increased slightly in the study group and decreased slightly in the control group . The use of cephalosporins increased slightly in both groups . CONCLUSION: Overall, academic detailing appeared to be no more effective in reducing antibiotic use than the practice-specific report cards alone. Am J Ophthalmol, 2004 Jun, 137(6), 1120 - 1 Subconjunctival antibiotics for acute postcataract extraction endophthalmitis--is it necessary? Iyer MN, Han DP, Yun HJ, Eastwood D, Kim JE, Connor TB, Wirostko WJ, Dev S. PURPOSE: To evaluate the efficacy of adjunctive subconjunctival antibiotic injection in the treatment of acute postcataract extraction endophthalmitis . DESIGN: Retrospective cohort study . METHODS: Patients who presented with hand motions or better vision and received subconjunctival antibiotics (SC+ group) were compared with those who did not (SC- group) in the treatment of acute postoperative endophthalmitis . RESULTS: The rate of obtaining a final vision of 20/40 or better was 60% in the SC+ group (n = 25) compared with 72% in the SC- group (n = 18) (P =.69), and the mean change in logMAR was -1.36 (improvement) versus -1.34 (P =.93) . Based on a linear regression model controlling for presenting vision, there was no statistical difference in the mean logMAR change between the two groups (P =.73) . CONCLUSION: Subconjunctival antibiotic injection as an adjunct to intravitreal antibiotics was unassociated with treatment benefit in patients with acute postoperative endophthalmitis presenting with vision of hand motions or better. Cutis, 2004 May, 73(5 Suppl), 10 - 4 Antibiotics: what's new? LaRosa SP, Tomecki KJ. In addition to the traditional antibiotic choices for skin and skin structure infections, such as beta-lactams, macrolides, and clindamycin, newer broad-spectrum antibiotics are available to treat resistant pathogens that can cause severe infections . The pharmacologic profiles of 3 newer classes of these antibiotics are reviewed briefly, and the role of these agents in treating skin and skin structure infections is discussed. Curr Med Chem, 2004 Jun, 11(12), 1645 - 56 Polyene macrolide antibiotic biosynthesis; Aparicio JF et al.; Polyenes constitute a large class of natural metabolites produced by giant multifunctional enzymes in a process resembling fatty acid biosynthesis . Like fatty acids, polyene macrolides and other polyketides are assembled by decarboxylative condensations of simple carboxylic acids . But while fatty acid intermediates are fully reduced, polyene macrolide intermediates suffer the suppression of reduction or dehydration reactions at given biosynthetic steps . In the last years, much progress has been made in our understanding of the linear and modular organization of the gene clusters, and the enzymes encoded by them, responsible for the biosynthesis of these macrocyclic metabolites . This know-how about the rules that govern polyene chain growth has provided the basis for the first rational manipulations of these fascinating systems for the production of engineered derivatives and promises a new era of novel polyene development, which will hopefully yield new molecules with improved pharmacological properties. Environ Toxicol Chem, 2004 May, 23(5), 1136 - 44 Fate of veterinary antibiotics in a macroporous tile drained clay soil; Kay P et al.; The environment may be exposed to veterinary medicines administered to livestock through the application of organic fertilizers to land . For other groups of substances that are applied to agricultural land (e.g., pesticides), preferential flow in underdrained clay soils has been identified as an extremely important mechanism by which pollution of surface waters can occur . This study, therefore, was performed to investigate the fate of three antibiotics from the sulfonamide, tetracycline, and macrolide groups . Pig slurry was applied to a field in arable production in two consecutive years and the fate of the compounds was monitored in the soil and drainage water . Both sulfachloropyridazine and oxytetracycline were detected in soil at concentrations up to 365 and 1691 microg/kg, respectively . Subsequently, peak concentrations of the two substances in drainflow were 613.2 and 36.1 microg/L, although mass losses to the receiving water were less than 0.5% . In contrast, tylosin was not detected at all . These findings could be explained by the persistence and sorption characteristics of the antibiotics, while preferential flow via desiccation cracks and worm channels to the tile drains was found to be the most important route for translocation of the chemicals . Thus, when the soil was disced prior to slurry application, losses were reduced significantly . It is evident that processes governing pesticide fate also apply to veterinary antibiotics. Gastroenterol Clin North Am, 2004 Jun, 33(2), 335 - 45, x Treatment of inflammatory bowel disease with antibiotics; Isaacs KL et al.; Although antibiotics are clearly recognized as having a role in treating the infectious complications of inflammatory bowel diseases (IBD), their impact in the primary treatment of IBD has long been an area of speculation . Over the past decade there is increasing evidence that luminal gut bacteria play a role in the pathogenesis of IBD, particularly Crohn's disease . Compelling evidence that normal commensal bacteria induce chronic intestinal inflammation in susceptible rodents provides an excellent rationale for treatment of human IBD with antibiotics . This article summarizes published studies of antibiotics in IBD patients and reviews available data for the use of antibiotic therapy in Crohn's disease and ulcerative colitis. Eur Respir J, 2004 May, 23(5), 671 - 8 Suppression of matrix metalloproteinase production from nasal fibroblasts by macrolide antibiotics in vitro; Kanai K et al.; It is well known that low-dose and long-term administration of macrolide antibiotics favourably modify the clinical status of chronic airway inflammatory diseases . However, the therapeutic mode of action of macrolide antibiotics is not well understood . The present study aimed to examine the influence of macrolide antibiotics, roxithromycin (RXM) and josamycin (JM) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts (NPF) in vitro . NPF, at a concentration of 2.5 x 10(5) cells x mL(-1), were stimulated with tumour necrosis factor (TNF)-alpha in the presence of various concentrations of RXM or JM for 24 h . MMP-2 and -9 levels in culture supernatants were analysed by ELISA, and MMP mRNA expression was examined by RT-PCR . The influence of RXM on nuclear factor (NF)-kappaB and activator protein (AP)-1 activation was also examined . Addition of RXM (but not JM) at 5.0 and 7.5 microg x mL(-1) significantly suppressed the production of MMP-2 and -9 from NPF induced by TNF-alpha stimulation . RXM also suppressed MMP mRNA expression through the inhibition of NF-kappaB and AP-1 activation . The present results suggest that the suppressive activity of roxithromycin on MMP-2 and -9 production is, in part, responsible for the therapeutic action of macrolides on chronic airway inflammatory diseases.
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