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