Antibiot Khimioter, 2003, 48(12), 5 - 8 {Effect of perfluoroorganic compounds on growth of streptomycetes and biosynthesis of antibiotic daunorubicin}; Bakulin MK et al.; The use of perfluoroorganic compounds, i.e . perfluorodecalin and "Perftoran", a blood substitute with the gas transfer function, known as "blue blood" (containing 3 vol . % of perfluoromethylcyclohexylpiperidin and 7 vol . % of perfluorodecalin as emulsion with the average particle size of 0.07 microns) in biotechnology for intensification of the Streptomyces purpurogeniscleroticus growth under submerged conditions was shown promising for the first time . An increase of the biomass output and higher yields of daunorubicin were also demonstrated. Semin Pediatr Infect Dis, 2004 Jan, 15(1), 41 - 51 Promoting appropriate antibiotic use for pediatric patients: a social ecological framework; Weissman J et al.; During the 1990s, the number of prescriptions for antibiotics for children and adolescents finally decreased after more than a decade of alarming increases . The Centers for Disease Control and Prevention (CDC) and many other groups have designed and implemented interventions to promote appropriate prescribing of antibiotics, and these efforts appear to have contributed to recent decreases in rates of such prescribing . In this article, we describe the various types of interventions that the CDC and others are using to encourage appropriate use of antibiotics . A social ecological framework is used to describe the various factors contributing to prescribing and using antibiotics, as well as the interventions used for targeting these factors . Although most efforts promoting appropriate use of antibiotics have focused on reducing such use for viral infections, future efforts also should include a focus on ensuring the use of targeted agents when antibiotics are indicated. J Oral Maxillofac Surg, 2004 Jun, 62(6), 708 - 13 The effect of high local concentrations of antibiotics on demineralized bone induction in rats; Kim SG et al.; PURPOSE: This study evaluated the effect of high local concentrations of antibiotics on bone repair induced by demineralized bone in rats . MATERIALS AND METHODS: Seventy-two 3-week-old rats, weighing 200 to 300 g, were used for the experiment . Rats were divided into 4 groups: control group (group 1), saline-impregnation group (group 2), gentamicin-impregnation group (group 3), and tetracycline-impregnation group (group 4) . The rats were killed at 3, 8, and 12 weeks after surgery . Samples were stained with hematoxylin-eosin and subjected to the histomorphometric analyses . RESULTS: There were significant differences in new bone formation among groups at all time periods . Comparing differences between groups at each time point, significantly more new bone formation was present in group 2 than in group 1 at 3 weeks, more in group 2 than in group 1 and more in group 2 than in group 4 at 8 weeks, and the most in group 2 among all groups at 12 weeks . In terms of the time period, significantly more new bone formation was observed at 8 weeks during the time period between 3 and 8 weeks, and at 12 weeks during the time period between 3 and 12 weeks . CONCLUSIONS: Our result suggests that the bone graft material is most effective when mixed with saline for the regeneration of osseous defects. Biosci Biotechnol Biochem, 2004 May, 68(5), 1106 - 12 Isolation of flavohemoglobin from the actinomycete Streptomyces antibioticus grown without external nitric oxide stress; Sasaki Y et al.; A flavocytochrome protein was isolated from the actinomycete Streptomyces antibioticus . The purified protein contained protoheme and FAD, and its M(r) was estimated to be 52000 . The absorption spectra in its resting oxidized, dithionite-reduced, carbon monoxide-bound, and oxygenated (O(2)-bound) forms were characteristic of those of flavohemoglobin (Fhb) . The N-terminal amino acid sequence showed high identities to those of other Fhb's . Furthermore, the actinomycete flavocytochrome scavenged nitric oxide in the presence of NADH . These results demonstrated that the flavocytochrome is the first Fhb purified from actinomycetes . The actinomycete Fhb was produced in S . antibioticus cells in large amounts without any external nitric oxide (NO) stress, which is indicative of a physiological function of Fhb other than detoxification of NO. J Spinal Disord Tech, 2004 Jun, 17(3), 243 - 7 Lumbar discography: should we use prophylactic antibiotics? A study of 435 consecutive discograms and a systematic review of the literature; Willems PC et al.; BACKGROUND: Lumbar discography can be used in the diagnostic work-up of degenerative spine disease . The most serious complication is discitis, believed to be due to penetration of the disc by a needle contaminated with skin flora . The use of prophylactic antibiotics has been advocated, although there is great concern regarding their efficacy and possible adverse effects on disc cells . METHODS: In the current study, the incidence of postdiscography discitis without the use of prophylactic antibiotics was studied in a consecutive patient group . Additionally, a systematic literature review was performed using strict criteria: 1) . Discography was performed by means of a two-needle technique, 2) . complications such as discitis were specifically looked for at follow-up, and 3) . the exact numbers of patients and those lost to follow-up were reported . RESULTS: The clinical results of 200 patients with 100% follow-up for a minimum period of 3 months showed no case of discitis . In the literature review, 10 studies were selected . Nine studies without prophylactic antibiotics reported an overall incidence of 12 cases in 4891 patients (0.25%) or 12770 discs (0.094%) . The only study with prophylactic antibiotics (127 patients) showed no case of discitis . CONCLUSIONS: Regarding the small number of patients in the only study in which antibiotics were used and the overall low incidence of postdiscography discitis, not enough evidence was found that prophylactic antibiotics can prevent discitis . It was concluded that in lumbar discography by means of a two-needle technique without prophylactic antibiotics, the risk of postdiscography discitis is minimal and there is not enough support from the literature to justify the routine use of prophylactic antibiotics. FEBS Lett, 2004 Jun 1, 567(1), 20 - 6 Ribosomal crystallography: a flexible nucleotide anchoring tRNA translocation, facilitates peptide-bond formation, chirality discrimination and antibiotics synergism; Agmon I et al.; The linkage between internal ribosomal symmetry and transfer RNA (tRNA) positioning confirmed positional catalysis of amino-acid polymerization . Peptide bonds are formed concurrently with tRNA-3' end rotatory motion, in conjunction with the overall messenger RNA (mRNA)/tRNA translocation . Accurate substrate alignment, mandatory for the processivity of protein biosynthesis, is governed by remote interactions . Inherent flexibility of a conserved nucleotide, anchoring the rotatory motion, facilitates chirality discrimination and antibiotics synergism . Potential tRNA interactions explain the universality of the tRNA CCA-end and P-site preference of initial tRNA . The interactions of protein L2 tail with the symmetry-related region periphery explain its conservation and its contributions to nascent chain elongation. Respir Care, 2004 Jun, 49(6), 635 - 9 Aerosolized antibiotics in mechanically ventilated patients; Smaldone GC; Aerosolized antibiotics are potentially useful in intensive care . At State University of New York at Stony Brook we developed a human model of tracheobronchitis in intubated patients . The model provides daily specimens of airway secretions, allowing serial studies of airway inflammation and testing of therapy modes . The presence of local infection is defined by a unique method of quantified sputum collection . Bench models have been developed that illustrate the factors that limit aerosol delivery to intubated patients . With those models clinical trials have defined possible indications for targeted aerosol therapy to patients at risk for deep lung infection . An efficient aerosolized-antibiotics method that delivers the aerosol past the endotracheal tube has been established, and with that method the drug levels in pulmonary secretions exceed by several orders of magnitude the levels expected with intravenous therapy . Potential end points of therapy are being evaluated, including the rate of bacterial resistance and the incidence and definition of deep lung infection. Helicobacter, 2004 Jun, 9(3), 278 - 83 Lower prevalence of Helicobacter pylori infection in patients with inflammatory bowel disease but not with chronic obstructive pulmonary disease - antibiotic use in the history does not play a significant role; Pronai L et al.; BACKGROUND: Patients with inflammatory bowel disease have lower prevalence of Helicobacter pylori infection, but the exact reason for this is not yet clear . AIM: To examine whether the antibiotics frequently used in inflammatory bowel disease are responsible for the lower prevalence of H . pylori infection . Patients with chronic obstructive pulmonary disease on prolonged previous antibiotic therapy were used for comparison . METHODS: Presence/absence of H . pylori infection was detected by a (13)C-urea breath test in 133 patients with inflammatory bowel disease (82 ulcerative colitis, and 51 Crohn's disease) and compared with that of 135 patients with chronic obstructive pulmonary disease and with two age-matched control groups (200 patients each) . Primary disease location, duration of disease and detailed analysis of previous and current medication (dose and duration of antibiotics, steroids, 5-aminosalicylic acid) were analysed in each cases . RESULTS: Seventeen of the 133 patients with inflammatory bowel disease {12.2% (10/82) of ulcerative colitis and 13.7% (7/51) of Crohn's disease} and 90/135 patients with chronic obstructive pulmonary disease (66.7%) were positive for H . pylori . A total of 78/200 (39%) for the inflammatory-bowel-disease-group-matched controls and 110/210 (55%) for the chronic-obstructive-pulmonary-disease-matched controls were positive for H . pylori . The history of any antibiotic or steroid therapy had no influence on H . pylori status of patients with inflammatory bowel disease . CONCLUSION: The prevalence of H . pylori compared to the age-matched controls is significantly lower in patients with inflammatory bowel disease but not in those with chronic obstructive pulmonary disease . Antibiotic use is not responsible for the lower prevalence of H . pylori infection in patients with inflammatory bowel disease. Int J Antimicrob Agents, 2004 Mar, 23(3), 213 - 7 Mechanisms of antibiotic neurotoxicity in renal failure; Chow KM et al.; Neurological complications of antibiotics are relatively common in renal failure . Central nervous system neurotoxicity due to penicillin and beta-lactam antibiotics is best documented with fewer accounts of ototoxicity, peripheral nerve toxicity and neuromuscular blockade . In the context of risk stratification, the goal of this review is to explore the mosaic of factors in renal impairment that may contribute to susceptibility to antibiotic neurotoxicity . Improved knowledge of the pathogenesis of these formidable adverse events among the renal failure subjects should help prevent antibiotic neurotoxicity in the future. Acta Radiol, 2004 Feb, 45(1), 13 - 7 Intermittent hepatic artery antibiotic infusion therapy for pyogenic hepatic abscess; Matoba M et al.; PURPOSE: To study the efficacy and problems associated with intermittent hepatic artery antibiotic infusion therapy for pyogenic hepatic abscess . MATERIAL AND METHODS: The material comprised eight patients with pyogenic hepatic abscess in whom percutaneous drainage could not be performed and intravenous administration of antibiotics was ineffective . An injection catheter was introduced into the common hepatic artery . Almost the same dose of antibiotics as with intravenous administration was infused intra-arterially 2-4 times per day . RESULTS: A therapeutic effect was achieved in six of the eight cases . In these 6 cases, the mean period of intra-arterial infusion was 10.8 days, while the mean period of catheter placement was 14.7 days . Using broad spectrum antibiotics, the therapeutic effect was obtained regardless of the numbers, morphologic characteristics, and differences in location of the abscesses . No significant complications were noted except in one case of splenic infarction . CONCLUSION: Intermittent hepatic artery antibiotic infusion therapy is useful as an alternative therapeutic procedure for pyogenic hepatic abscess in which percutaneous drainage cannot be performed and intravenous administration of antibiotics is ineffective. Antibiot Khimioter, 2004, 49(1), 4 - 7 {Development of new technology for isolation of nebramycin complex antibiotics from the cultural fluid}; Nogovitsyna LV et al.; A new technology for nebramycin complex antibiotics isolation from non-filtered culture fluid was developed . The industrial use of the technology permitted to exclude the stage of the culture fluid filtration, to increase the yield by more than 33% and to reduce the time of the process by 1.7 times. J Agric Food Chem, 2004 Jun 2, 52(11), 3231 - 6 Development of a fluorescent latex immunoassay for detection of a spectinomycin antibiotic; Medina MB; There is a need to develop a rapid and sensitive method to detect spectinomycin residues in animal tissues . A latex fluorescent immunoassay was designed using reagents developed for this assay . The spectinomycin antibody was produced in sheep, and the immunoglobulin (IgG) was purified through a Protein G affinity column and was immobilized onto latex particles . Spectinomycin was labeled with 5-({4,6-dichlorotriazin-2-yl}amino)fluorescein (DTAF) . The optimum assay conditions consisted of preincubating the latex-IgG with spectinomycin in buffer solutions or in bovine kidney extracts . DTAF-spectinomycin was added and was further incubated . The bound spectinomycin-DTAF/IgG-latex complex was separated by centrifugation at 4000 g for 10 min . The fluorescence signals of the unbound spectinomycin-DTAF in the supernatant were measured at 485/535 nm excitation/emission . The measured signals were directly proportional to the concentration of spectinomycin in the samples, and spectinomycin was detected at 0-100 ppb with minimum detectability of 5 ppb . The mean regression correlation of four trials in buffer was 0.936 when the % bound complex vs spectinomycin concentration was plotted . Analysis of the kidney extract spiked with 0-100 ppb spectinomycin had a regression correlation of 0.959 . This assay provides a rapid screening method for low ppb detection of spectinomycin. Clin Infect Dis, 2004 May 15, 38(10), 1401 - 8 Epub 2004 Apr 29. Sedation, sucralfate, and antibiotic use are potential means for protection against early-onset ventilator-associated pneumonia; Bornstain C et al.; To examine risk factors for early-onset ventilator-associated pneumonia (EOP) in patients requiring mechanical ventilation (MV), we performed a prospective cohort study that included 747 patients . Pneumonia was defined as a positive result for a protected quantitative distal sample . EOP was defined as pneumonia that occurred from day 3 to day 7 of MV . Eighty patients (10.7%) experienced EOP . Independent predictors of EOP were male sex (odds ratio {OR}, 2.06; 95% confidence interval {CI}, 1.18-3.63), actual Glasgow Coma Scale value of 6-13 (OR, 1.95; 95% CI, 1.2-3.18), high Logistic Organ Dysfunction score at day 2 (OR, 1.12 per point; 95% CI, 1.02-1.23), unplanned extubation (OR, 3.19; 95% CI, 1.28-7.92), and sucralfate use (OR, 1.81; 95% CI, 1.01-3.26) . Protection occurred with use of aminoglycosides (OR, 0.36; 95% CI, 0.17-0.76), beta -lactams and/or beta -lactamase inhibitors (OR, 0.47; 95% CI, 0.28-0.83), or third-generation cephalosporins (OR, 0.33; 95% CI, 0.16-0.74) . Sucralfate use and unplanned extubation are independent risk factors for EOP . Use of aminoglycosides, beta-lactams/ beta-lactamase inhibitors, or third-generation cephalosporins protects against EOP. J Econ Entomol, 2004 Apr, 97(2), 171 - 6 Larval Apis mellifera L . (Hymenoptera: Apidae) mortality after topical application of antibiotics and dusts; Pettis JS et al.; Beekeepers apply various dusts to honey bee, Apis mellifera L., colonies to dislodge parasitic mites and control bacterial brood diseases . Anecdotal reports by beekeepers indicate that the antibiotic oxytetracycline (OTC) can be toxic when applied in powdered sugar to cells containing immature bee brood, but it was not known whether the purported toxicity is caused by the antibiotic or the sugar carrier . Additionally, the toxicity of various dusts, proposed for parasitic mite control, is poorly known . In the current studies, we tested OTC and two other antibiotics (tylosin and lincomycin, candidate compounds for use in honey bee colonies) in a powdered sugar carrier for larval toxicity . We also tested for larval toxicity, several dusts that have been proposed for mite control . OTC caused significant brood mortality of approximately 80% at the concentrations used in the hive (200 mg in 20 g sugar) . In contrast, tylosin and lincomycin at the 200 mg dose were both similar to untreated controls, and only five times that concentration (1000 mg) caused significant brood mortality of approximately 65% . The addition of dusts, wheat flour, talc, and a commercially available protein supplement, BeePro, resulted in mortality levels between 65 and 80%, similar to that seen with OTC . The common antibiotic carrier, powered confectioners sugar, was nontoxic . The use of 100 unsealed brood cells was demonstrated to be a reliable means of assessing potential adverse affects of dry compounds on larval honey bees . Two new candidate antibiotics for use in honey bee colonies were less toxic to larval bees than the currently labeled antibiotic, OTC. J Clin Pharm Ther, 2004 Jun, 29(3), 231 - 9 Appropriate antibiotic utilization in seniors prior to hospitalization for community-acquired pneumonia is associated with decreased in-hospital mortality; Johnson D et al.; BACKGROUND: We analysed the association of mortality and prescription of antibiotics prior to hospitalization for community-acquired pneumonia . METHODS: We used administrative data (hospital abstracts, physician claims, prescriptions) for seniors (age 61 years and over) for Alberta, Canada from 1 April 1994 to 31 March 1999 . RESULTS: Hospitalization of 21 191 seniors occurred during the study period . In about 43% of hospitalizations (n = 9034), a physician was consulted prior to hospital admission . Antibiotics were dispensed to 31% of those with a prior physician visit and in about 72%, the antibiotic choice was deemed appropriate . The odds for mortality were significantly decreased in those with prior physician visits (OR = 0.87, P < 0.01), with any antibiotic prescription (OR = 0.66, P < 0.0001), and with an appropriate antibiotic (OR = 0.68, P = 0.03) . The choice of an appropriate antibiotic as opposed to an inappropriate antibiotic resulted in a 2.6% absolute and 38% relative mortality reduction . CONCLUSION: Choosing an appropriate outpatient antibiotic in accordance with published expert opinion guidelines compared with inappropriate antibiotic prescriptions decreased hospital mortality in patients subsequently hospitalized for community-acquired pneumonia. J Gastroenterol Hepatol, 2004 Jun, 19(6), 619 - 25 Use of imidazole-based eradication regimens for Helicobacter pylori should be abandoned in North India regardless of in vitro antibiotic sensitivity; Bhatia V et al.; BACKGROUND AND AIM: The purpose of this study was to compare the efficacy of tinidazole- versus clarithromycin-based triple regimens for eradication of Helicobacter pylori in North Indian patients of peptic ulcer disease, and to correlate the outcome with in vitro antibiotic susceptibility . METHODS: One hundred and forty-six H . pylori-infected patients with active ulcer were included in the prospective, randomized study . A total of 70 patients received lansoprazole 30 mg b.d., amoxycillin 1000 mg b.d . and tinidazole 500 mg b.d . (LAT), and 76 patients received lansoprazole 30 mg b.d., amoxycillin 1000 mg b.d . and clarithromycin 500 mg b.d . (LAC) for 14 days . The H . pylori status was assessed by urea breath test, rapid urease test, and histology and antibiotic sensitivity pattern by Epsilometer test . RESULTS: In per-protocol analysis of 112 patients the H . pylori eradication rate was 42.3% (95% confidence interval (CI): 0.29-0.56) in LAT, and 64.8% (95%CI: 0.52-0.78) in LAC (95%CI of difference of proportions: 0.13-0.33, P = 0.01) . Ulcer healed in 69.2% in the LAT group (95%CI: 0.57-0.82) and 81.7% in the LAC group (95%CI: 0.72-0.92; P = 0.02) . Antibiotic susceptibility testing was done in 31 patients . Metronidazole resistance was present in 41.9% isolates but was unrelated to the outcome of the LAT regimen . CONCLUSION: Imidazole-based eradication regimens should be abandoned in North India regardless of in vitro susceptibility results. Orthopade, 2004 Jul, 33(7), 817 - 21 {Characterization of custom-made biomaterials containing antibiotics}; Pfefferle HJ et al.; The aim of this study was to evaluate the quality of custom-made antibiotic carriers which are produced for hospitals in a central service laboratory . These sterile products, made according to antibiogram, showed quality parameters which are comparable with commercially available products in terms of antibiotic release and other relevant properties. ANZ J Surg, 2004 May, 74(5), 324 - 9 Protocol-based approach to suspected appendicitis, incorporating the Alvarado score and outpatient antibiotics; Winn RD et al.; BACKGROUND: There is evidence that antibiotics can be used as primary treatment for appendicitis, however, delayed surgical treatment might still be associated with perforation . Most patients at risk of perforation have high Alvarado scores . We designed a protocol-based approach to suspected appendicitis, in which the Alvarado score was used to select patients for early treatment with surgery or outpatient antibiotics . METHODS: Patients included in the present study were adults and children referred to the surgical service at John Hunter Hospital (Newcastle, Australia) with suspected appendicitis in the 12 months from July 2000 . Treatment groups: no treatment (Alvarado score 1-4); antibiotics alone (Alvarado 5-7); early surgery (Alvarado 8-10) . Outcome measures: time to operation; duration of hospital stay; non-therapeutic operations; delayed treatment in association with perforation; recurrent appendicitis (for those treated with antibiotics) . Comparison group: 142 patients managed with 'best clinical practice' as part of an earlier trial . RESULTS: One hundred and twenty-two patients were enrolled . Median time to operation was 3.9 h (comparison group 7.3 h, P = 0.014) . Median length of stay was 38.5 h (comparison group 44.2 h, P = 0.041) . There were two cases of delayed treatment in association with perforation (2/122 = 1.6%, comparison group 2/142 = 1.4%, P = 0.88) and 10 non-therapeutic operations (10/122 = 8.1%, comparison group 15/142 = 10.6%, P = 0.51) . Of those whose initial illness was treated successfully with antibiotics, 2/42 (4.8%) subsequently required appendicectomy . CONCLUSIONS: This protocol-based approach to suspected appendicitis is feasible . A prospective controlled study would be required to confirm potential benefits (in terms of short hospital stay) and to confirm that there is not an increase in adverse outcomes. Mol Cancer Ther, 2004 May, 3(5), 577 - 85 DNA damage responses triggered by a highly cytotoxic monofunctional DNA alkylator, hedamycin, a pluramycin antitumor antibiotic; Tu LC et al.; Long-term exposure (72 h) to hedamycin, a monofunctional DNA alkylator of the pluramycin class of antitumor antibiotics, decreased growth of mammalian cells by 50% at subnanomolar concentrations . Short-term treatment (4 h) rapidly reduced DNA synthesis by 50% also at subnanomolar concentrations, but substantially higher levels were needed to block RNA synthesis while protein synthesis even at very high hedamycin concentrations remained unaffected . Hedamycin treatment at concentrations below its growth IC(50) induced only a transient and temporary accumulation of cells in G(2) . Somewhat higher concentrations resulted in substantial S-phase arrest, and at increasing concentrations, complete cell cycle arrest in G(1) was observed without the appearance of a sub-G(1) cell population . Neither inhibition of cell growth nor cell cycle arrest appeared to be dependent on ataxia and Rad-related kinase expression . DNA damage checkpoint proteins including p53, chk1, and chk2 were differentially activated by hedamycin depending on the concentration and duration of treatment . The level of downstream cell cycle regulators such as cdc25A, E2F1, cyclin E, and p21 were also altered under conditions that induced cell cycle arrest, but atypically, p21 overexpression was observed only in S-phase-arrested cells . Apoptotic indicators were only observed at moderate hedamycin concentrations associated with S-phase arrest, while increasing concentrations, when cells were arrested in G(1), resulted in a reduction of these signals . Taken together, the responses of cells to hedamycin are distinct with regard to its effect on cell cycle but also in the unusual concentration-dependent manner of activation of DNA damage and cell cycle checkpoint proteins as well as the induction of apoptotic-associated events. J Inorg Biochem, 2004 May, 98(5), 720 - 6 The effect of metal ions on the electrochemistry of the antitumor antibiotic streptonigrin; Anderberg PI et al.; The effect of transition metal ions on the electrochemistry of 6-methoxy-5,8-quinolinedione (L(1)), 7-amino-6-methoxy-5,8-quinolinedione (L(2)) and the antitumor antibiotic streptonigrin (SN) was studied . In 10% methanol/water, the one-electron reduction of quinones L(1) and L(2) to the corresponding semiquinones is shifted to more positive potentials upon addition of one equivalent of Zn(II), Ni(II), Co(II) or Cd(II) and is consistent with formation of a 1:1 complex involving the quinone(N) and adjacent quinone(O) . Similar results are observed for Cu(II) and Mn(II), but the redox chemistry is also complicated by metal-based redox chemistry . The addition of further equivalents of M(II) results in a number of different coordination and electrochemical processes including formation of 1:1 and 2:1 complexes of the quinone, semiquinone and dianion . Under similar conditions, the 1:1 SN 2, {Formula: see text} -bipyridyl metal complex undergoes a reversible one-electron reduction to the semiquinone . The redox potential of the quinone in SN was shifted positive in the presence of the metal ions, but both the magnitude of the shift, and the relative influence of the metals was different to ligands L(1) and L(2) . The changes in redox chemistry of SN compared with L(1) and L(2) are consistent with the formation of the 2, {Formula: see text} -bipyridyl complexes in which there is weaker coordination to the quinone(O) in ring A of SN . These results suggest that in vivo, metal ions such as Zn(II), Cu(II) and Mn(II) facilitate the initial reduction of streptonigrin to the semiquinone by capturing the semiquinone after SN is reduced by biological reductants. Biol Pharm Bull, 2004 May, 27(5), 641 - 6 General pharmacology of DW-286a, a new fluoronaphthyridone antibiotic: effects on central nervous, cardiovascular, and respiratory systems; Kim EJ et al.; DW-286a is a new class of fluoronaphthyridone antibiotic . Its effect on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied . The doses given were 30, 50, 100, 150, 300, and 1000 mg/kg and drugs were administered orally . DW-286a did not show any effects on general behavior, motor coordination, analgesic action, seizure and mortality, blood pressure and heart rate, contractile response of isolated guinea pig ileums, and renal function . On the other hand, DW-286a decreased spontaneous locomotor activity from 120 to 240 min after administration at the doses of 300 and 1000 mg/kg and the respiration rate from 30 to 240 min after the administration of doses up to 100 mg/kg . The sleeping time and body temperature were increased significantly in mice at the dose of 1000 mg/kg . DW-286a increased the charcoal transport significantly at doses of 300 and 1000 mg/kg . DW-286a inhibited gastric acid secretion, reduced the volume of the gastric juice and total acidity, and increased the pH dose dependently . Based on the above results, it was concluded that DW-286a affects spontaneous locomotor activity, respiration and body temperature, gastrointestinal transport, gastric secretory action, and hexobarbital sleeping time at high doses. J Clin Microbiol, 2004 May, 42(5), 2252 - 4 Collaborative study of antibiotic medium 3 and flow cytometry for identification of amphotericin B-resistant Candida isolates; Chaturvedi V et al.; Center 1 used the National Committee for Clinical Laboratory Standards M27-A2 method and antibiotic medium 3 (AM3) test to determine amphotericin B resistance in 5 of 30 Candida isolates . These isolates were tested at center 2 by AM3 test and flow cytometry (FC) . The agreements (C1-C2) were 90% for AM3 test and FC and 73% for the AM3 tests. Int J Pediatr Otorhinolaryngol, 2004 Mar, 68(3), 373 - 8 Pott's puffy tumour in a pre-adolescent child: the youngest reported in the post-antibiotic era; Gupta M et al.; Pott's puffy tumour is a subperisosteal abscess associated with a cranial osteomyelitis . A rare consequence of trauma or frontal sinusitis, it is often an indicator of intracranial complications . At 3 years of age, the patient described is the youngest reported with this condition . The occurrence of such pathology in pre-adolescent children is very rare and this case is one of three reported in the English literature in the post-antibiotic era. J Antimicrob Chemother, 2004 Jun, 53(6), 1062 - 7 Epub 2004 May 05. Improving appropriateness of antibiotic therapy: randomized trial of an intervention to foster reassessment of prescription after 3 days; Senn L et al.; OBJECTIVES: Reassessment of ongoing antibiotic therapy is an important step towards appropriate use of antibiotics . This study was conducted to evaluate the impact of a short questionnaire designed to encourage reassessment of intravenous antibiotic therapy after 3 days . PATIENTS AND METHODS: Patients hospitalized on the surgical and medical wards of a university hospital and treated with an intravenous antibiotic for 3-4 days were randomly allocated to either an intervention or control group . The intervention consisted of mailing to the physician in charge of the patient a three-item questionnaire referring to possible adaptation of the antibiotic therapy . The primary outcome was the time elapsed from randomization until a first modification of the initial intravenous antibiotic therapy . It was compared within both groups using Cox proportional-hazard modelling . RESULTS: One hundred and twenty-six eligible patients were randomized in the intervention group and 125 in the control group . Time to modification of intravenous antibiotic therapy was 14% shorter in the intervention group (adjusted hazard ratio for modification 1.28, 95% CI 0.99-1.67, P = 0.06) . It was significantly shorter in the intervention group compared with a similar group of 151 patients observed during a 2 month period preceding the study (adjusted hazard ratio 1.17, 95% CI 1.03-1.32, P = 0.02) . CONCLUSION: The results suggest that a short questionnaire, easily adaptable to automatization, has the potential to foster reassessment of antibiotic therapy. J Bacteriol, 2004 May, 186(10), 3259 - 61 Lipid II-mediated pore formation by the peptide antibiotic nisin: a black lipid membrane study; Wiedemann I et al.; The antibiotic peptide nisin is the first known lantibiotic that uses a docking molecule within the bacterial cytoplasmic membrane for pore formation . Through specific interaction with the cell wall precursor lipid II, nisin forms defined pores which are stable for seconds and have pore diameters of 2 to 2.5 nm. J Bacteriol, 2004 May, 186(10), 3160 - 72 Organization and expression of the polynucleotide phosphorylase gene (pnp) of Streptomyces: Processing of pnp transcripts in Streptomyces antibioticus; Bralley P et al.; We have examined the expression of pnp encoding the 3'-5'-exoribonuclease, polynucleotide phosphorylase, in Streptomyces antibioticus . We show that the rpsO-pnp operon is transcribed from at least two promoters, the first producing a readthrough transcript that includes both pnp and the gene for ribosomal protein S15 (rpsO) and a second, Ppnp, located in the rpsO-pnp intergenic region . Unlike the situation in Escherichia coli, where observation of the readthrough transcript requires mutants lacking RNase III, we detect readthrough transcripts in wild-type S . antibioticus mycelia . The Ppnp transcriptional start point was mapped by primer extension and confirmed by RNA ligase-mediated reverse transcription-PCR, a technique which discriminates between 5' ends created by transcription initiation and those produced by posttranscriptional processing . Promoter probe analysis demonstrated the presence of a functional promoter in the intergenic region . The Ppnp sequence is similar to a group of promoters recognized by the extracytoplasmic function sigma factors, sigma-R and sigma-E . We note a number of other differences in rspO-pnp structure and function between S . antibioticus and E . coli . In E . coli, pnp autoregulation and cold shock adaptation are dependent upon RNase III cleavage of an rpsO-pnp intergenic hairpin . Computer modeling of the secondary structure of the S . antibioticus readthrough transcript predicts a stem-loop structure analogous to that in E . coli . However, our analysis suggests that while the readthrough transcript observed in S . antibioticus may be processed by an RNase III-like activity, transcripts originating from Ppnp are not . Furthermore, the S . antibioticus rpsO-pnp intergenic region contains two open reading frames . The larger of these, orfA, may be a pseudogene . The smaller open reading frame, orfX, also observed in Streptomyces coelicolor and Streptomyces avermitilis, may be translationally coupled to pnp and the gene downstream from pnp, a putative protease. J Int Acad Periodontol, 2004 Apr, 6(2), 47 - 55 Antibiotic prescription and dental practice within Saudi Arabia; the need to reinforce guidelines and implement specialty needs; Al-Mubarak S et al.; The aim of the present survey was to analyse the frequency and type of antibiotic prescriptions used in dental practice in Saudi Arabia, to assess the awareness of periodontal treatment need among dentists and specialists and to evaluate the distribution of dental specialties in Saudi Arabia . We distributed a questionnaire to 378 dentists including different specialists working in various major hospitals and dental departments . This same questionnaire was then redistributed, 3 years later, to 211 participants . Results from both surveys indicated that antibiotics were not always prescribed on a scientific basis . Cost was the most significant factor (p < 0.05) . Interestingly, and although periodontal disease was included as one of the possible causes of infections, the penicillin group was shown to be the group of choice (p < 0.007) and was prescribed by 45% of all participants, metronidazole and tetracyclines followed and were the second most commonly prescribed antibiotics in both surveys (p < 0.05) . It was further demonstrated that although the need for periodontics is present among patients and specialists, it is one of the least practised specialties (p < or = 0.008) along with oral surgery (p < or = 0.36). Int J Clin Pharmacol Ther, 2004 Apr, 42(4), 246 - 52 Patterns of systemic antibiotic use in a tertiary hospital in Israel in the years 1998-2000; Kitzes-Cohen R et al.; OBJECTIVES: To investigate the pattern of antibiotic use in the hospital over a 3-year period according to individual drugs and hospital departments . SETTING: 335 adult beds of a tertiary hospital in Northern Israel during the years 1998-2000 . An antibiotic control policy restricts the use of the most expensive antibiotics and those with broad spectrum of activity and a major impact on bacterial resistance . METHODS: The ATC/DDD and DU 90% methodologies were used . The use of antibiotics was expressed as the number of defined daily doses (DDD) per 100 bed-days . RESULTS: The total antibiotic use varied during the study period from 93.7-101.0 DDD/100 bed-days (p < 0.1) . Thirteen drugs accounted for 90% of the total volume . The use of broad spectrum penicillins was the highest of all drugs followed by cephalosporins and oral quinolones . The highest rates of antibiotic use were found in the departments of ENT, urology, gynecology and orthopedics and in the intensive care unit (ICU) . The total restricted antibiotics use was 7.2 DDD/100 bed-days and was the highest in the ICU . CONCLUSIONS: The ATC/DDD methodology provided delineation and interpretation of antibiotic usage patterns in the hospital . Although the overall use is higher then that found in several reports from European hospitals, stratification by individual drugs and by hospital department yielded similar trends. Chem Biol, 2004 Feb, 11(2), 195 - 201 Manipulation of carrier proteins in antibiotic biosynthesis; La Clair JJ et al.; Engineering biosynthetic pathways into suitable host organisms has become an attractive venue for the design, evaluation, and production of small molecule therapeutics . Polyketide (PK) and nonribosomal peptide (NRP) synthases have been of particular interest due to their modular structure, yet routine cloning and expression of these enzymes remains challenging . Here we describe a method to covalently label carrier proteins from PK and NRP synthases using the enzymatic transfer of a modified coenzyme A analog by a 4'-phosphopantetheinyltransferase . Using this method, carrier proteins can be loaded with single fluorescent or affinity reporters, providing novel entry for protein visualization, Western blot identification, and affinity purification . Application of these methods provides an ideal tool to track and quantify metabolically engineered pathways . Such techniques are valuable to measure protein expression, solubility, activity, and native posttranslational modification events in heterologous systems. Pediatrics, 2004 May, 113(5), e385 - 94 Racial/ethnic variation in parent expectations for antibiotics: implications for public health campaigns; Mangione-Smith R et al.; CONTEXT: Widespread overuse and inappropriate use of antibiotics are a major public health concern . Little is known about racial/ethnic differences in parents seeking antibiotics for their children's upper respiratory illnesses . OBJECTIVE: To examine racial/ethnic differences in parent expectations about the need for antibiotics and physician perceptions of those expectations . DESIGN: We conducted a nested, cross-sectional survey of parents who were coming to see their child's pediatrician because of cold symptoms between October 2000 and June 2001 . Parents completed a previsit survey that collected information on demographics, their child's illness, and a 15-item previsit expectations inventory that included an item asking how necessary it was for the physician to prescribe antibiotics . Physicians completed a postvisit survey that collected information on diagnosis, treatment, and whether the physician perceived the parent expected an antibiotic . The encounter was the unit of analysis . Multivariate logistic regression analyses were performed to evaluate predictors of dichotomized parental expectations for antibiotics, dichotomized physician perceptions of those expectations, diagnostic patterns, and antibiotic-prescribing patterns . SETTING: Twenty-seven community pediatric practices in the Los Angeles, Calif, metropolitan area . PARTICIPANTS: A volunteer sample of 38 pediatricians (participation rate: 64%) and a consecutive sample of 543 parents (participation rate: 83%; approximately 15 participating for each enrolled pediatrician) seeking care for their children's respiratory illnesses . Pediatricians were eligible to participate if they worked in a community-based managed care practice in the Los Angeles area . Parents were eligible to participate if they could speak and read English and presented to participating pediatricians with a child 6 months to 10 years old who had cold symptoms but had not received antibiotics within 2 weeks . MAIN OUTCOME MEASURES: Parental beliefs about the necessity of antibiotics for their child's illness, physician perceptions of parental expectations for antibiotics, bacterial diagnosis rates, and antibiotic-prescribing rates . RESULTS: Forty-three percent of parents believed that antibiotics were definitely necessary, and 27% believed that they were probably necessary for their child's illness . Latino and Asian parents were both 17% more likely to report that antibiotics were either definitely or probably necessary than non-Hispanic white parents . Physicians correctly perceived that Asian parents expected antibiotics more often than non-Hispanic white parents but underestimated the greater expectations of Latino parents for antibiotics . Physicians also correctly perceived that parents of children with ear pain or who were very worried about their child's condition were significantly more likely to expect antibiotics . Physicians were 7% more likely to make a bacterial diagnosis and 21% more likely to prescribe antibiotics when they perceived that antibiotics were expected . CONCLUSIONS: Parent expectations for antibiotics remain high in Los Angeles County . With time, traditional public health messages related to antibiotic use may decrease expectations among non-Hispanic white parents . However, both public health campaigns and physician educational efforts may need to be designed differently to reach other racial/ethnic groups effectively . Despite public health campaigns to reduce antibiotic overprescribing in the pediatric outpatient setting, physicians continue to respond to parental pressure to prescribe them . To effectively intervene to decrease rates of inappropriate antibiotic prescribing further, physicians need culturally appropriate tools to better communicate and negotiate with parents when feeling pressured to prescribe antibiotics. Int J Antimicrob Agents, 2004 May, 23(5), 446 - 50 Respiratory tract infections: diagnosis and use of antibiotics by family physicians in north-eastern Poland; Chlabicz S et al.; The aim of our study was to describe the pattern of antibiotic prescribing for respiratory tract infections . Forty-four family physicians from Bialystok (north-eastern Poland) filled in questionnaires regarding 1315 patients with respiratory tract infections . Antibiotics were prescribed in 803 cases (61.1%) . The four principle diagnoses associated with prescribing an antibiotic were: bacterial pharyngitis/tonsillitis, acute bronchitis, unspecified bacterial superinfection and acute sinusitis for which a total of 572 antibiotic treatments were given (71.2% of all antibiotic prescriptions) . The study shows that Polish family physicians diagnose respiratory tract infections empirically and frequently prescribe wide-spectrum antibiotics . More information is required about the diagnostic value of certain clinical symptoms such as purulent sputum, duration of cough and indications for broad-spectrum antibiotic use. Scand J Prim Health Care, 2004 Mar, 22(1), 16 - 21 Recurrent antibiotic use in a small child and the effects on the family; Louhi-Pirkanniemi K et al.; OBJECTIVE: To determine the typical characteristics of small children on recurrent therapy with antibiotics (RTA) and the effects RTA have on the families . DESIGN: Stratified randomised cluster sampling . SETTING: An unselected population-based questionnaire study in Finland . SUBJECTS: Parents (n = 1443) expecting their first child were followed prospectively from the mother's early pregnancy until the child was 18 months of age . MAIN OUTCOME MEASURES: The outcome measure was the number of courses of antibiotic therapy (options: 011-51 > or = 6) during the child's first 18 months of life . Six or more courses were considered RTA . Associated variables were child- and family-related factors during the child's first 18 months of life . RESULTS: Children on RTA were taken to see a physician more often than other children when they had fever or a common cold . RTA was significantly associated with the child's day care outside the home, allergy and need for a special diet . The father's severe stress was associated with the child's RTA . Breastfeeding lasting more than 3 months was found to have a protective effect against RTA . CONCLUSION: The threshold for seeking medical help was low in the families of children on RTA, which is best avoided by breastfeeding and day care at home . Health care staff should not forget to support families, especially the fathers, with children experiencing recurrent infections. Can Fam Physician, 2004 Apr, 50, 569 - 75 Antibiotics for lower respiratory tract infections . Still too frequently prescribed? McIsaac WJ, To T. OBJECTIVE: To examine how Canadian family physicians currently prescribe for lower respiratory tract infections (LRTIs) . DESIGN: Prospective assessment of adults with symptoms of LRTIs . SETTING: Offices of 120 community-based members of the College of Family Physicians of Canada . PARTICIPANTS: Four hundred seven adults (16 years and older) . MAIN OUTCOME MEASURES: Clinical findings, diagnoses, tests ordered, and prescriptions for antibiotics were documented on a standardized form . RESULTS: Antibiotics were prescribed to 58.4% of patients presenting with symptoms of LRTIs . Prescribing was higher (77.9%) for those diagnosed with acute bronchitis, which accounted for 70.3% of prescriptions . Physicians were often uncertain about the need for antibiotics, were concerned that patients could become sicker, and felt pressured by patients to prescribe antibiotics . Macrolides were most frequently prescribed; no tests were ordered in 85.0% of encounters . CONCLUSION: The number of antibiotic prescriptions for adults with LRTIs remains high in Canada . Rates of prescribing are increased by diagnosis of acute bronchitis, clinical uncertainty, pressure from patients to receive antibiotics, and concern that patients will deteriorate if left untreated. Chem Biol, 2004 Jan, 11(1), 107 - 19 Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase; Li TL et al.; The gene cluster encoding biosynthesis of the clinically important glycopeptide antibiotic teicoplanin has been cloned from Actinoplanes teichomyceticus . Forty-nine putative open reading frames (ORFs) were identified within an 89 kbp genetic locus and assigned roles in teicoplanin biosynthesis, export, resistance, and regulation . Two ORFs, designated orfs 1 and 10*, showed significant homology to known glycosyltransferases . When heterologously expressed in Escherichia coli, these glycosyltransferases were shown to catalyze the transfer of UDP-(N-acetyl)-glucosamine onto, respectively, 3-chloro-beta-hydroxytyrosine-6 (3-Cl-6betaHty) and 4-hydroxyphenylglycine-4 (4Hpg) of the teicoplanin heptapeptide aglycone . The product of another ORF, orf11*, was demonstrated in vitro to transfer n-acetyl-, n-butyryl-, and n-octanoyl-groups from acyl-CoA donors either to a free UDP-aminosugar or to an aminosugar moiety in the teicoplanin pseudoaglycone, thus identifying Orf11* as the key acyltransferase in teicoplanin maturation . These findings should accelerate the combinatorial engineering of new and improved glycopeptide drugs. Chem Biol, 2004 Jan, 11(1), 79 - 86 Cloning, sequencing, and functional analysis of the biosynthetic gene cluster of macrolactam antibiotic vicenistatin in Streptomyces halstedii; Ogasawara Y et al.; Vicenistatin, an antitumor antibiotic isolated from Streptomyces halstedii, is a unique 20-membered macrocyclic lactam with a novel aminosugar vicenisamine . The vicenistatin biosynthetic gene cluster (vin) spanning approximately 64 kbp was cloned and sequenced . The cluster contains putative genes for the aglycon biosynthesis including four modular polyketide synthases (PKSs), glutamate mutase, acyl CoA-ligase, and AMP-ligase . Also found in the cluster are genes of NDP-hexose 4,6-dehydratase and aminotransferase for vicenisamine biosynthesis . For the functional confirmation of the cluster, a putative glycosyltransferase gene product, VinC, was heterologously expressed, and the vicenisamine transfer reaction to the aglycon was chemically proved . A unique feature of the vicenistatin PKS is that the loading module contains only an acyl carrier protein domain, in contrast to other known PKS-loading modules containing certain activation domains . Activation of the starter acyl group by separate polypeptides is postulated as well. Chem Biol, 2004 Jan, 11(1), 8 - 10 Aureolic acids: similar antibiotics with different biosynthetic gene clusters; O'Connor S; In this issue of Chemistry & Biology, Mendez and colleagues describe the sequence and organization of the chromomycin gene cluster . Unexpectedly, the arrangement is starkly different from the mithramycin biosynthetic cluster, despite similarity in the individual genes and the near identical structures of the two antibiotic aureolic acids. Cochrane Database Syst Rev . 2004;(2):CD003143. Antibiotics / anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs; Badger C et al.; BACKGROUND: Lymphoedema is a chronic and progressive condition and current debate revolves around the best course of management for infective/inflammatory episodes . OBJECTIVES: To determine whether antibiotic/anti-inflammatory drugs given prophylactically reduce the number and severity of infective/inflammatory episodes in patients with lymphoedema . SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register in September 2003, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and the International Society of Lymphology congress proceedings . SELECTION CRITERIA: Types of studies considered for review were randomised controlled trials testing an antibiotic or anti-inflammatory drug against placebo (with or without physical therapies) . DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers who screened the papers independently using a checklist of criteria relating to the randomisation and blinding of a trial . Both reviewers extracted data from the eligible studies using a data extraction form . MAIN RESULTS: Overall, four studies (364 randomised patients) were included . Two of these studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the trial period in the treated group but one case of infection in the two placebo groups respectively during the first three weeks of each trial . Seven additional cases of infection in trial one and 14 cases in trial two required treatment in the three month follow up period.One anti filarial trial reported a total of 127 ADL episodes for all groups during the treatment year (compared with 684 episodes reported for the same participants during the pre-treatment year) . Another 228 ADL episodes were reported during the trial follow-up year but no significant differences were found between the three groups . No apparent link was found between the grade of oedema and the frequency of ADL episodes . However, there was a significant link between increased episodes and the rainy season . In the penicillin group the mean number of inflammatory episodes was reduced from 4.6 to 0.5 after treatment and increased to 1.9 at the end of the follow-up year . REVIEWERS' CONCLUSIONS: The effectiveness of selenium in preventing AIE in lymphoedema remains inconclusive in the absence of properly conducted randomised controlled trials . Anti-filarials (DEC and Ivermectin) do not appear to reduce ADL episodes in filarial lymphoedema . Foot care may be important in reducing ADL episodes, and penicillin appears to contribute to a significant reduction in ADL, when combined with foot-care . It seems reasonable to emphasise the importance of foot-care to patients and practitioners in preventing infection and this may also apply to care of the arm in women who develop lymphoedema following breast cancer treatment . However, properly conducted trials are needed to demonstrate any efficacy of these interventions. Antimicrob Agents Chemother, 2004 May, 48(5), 1652 - 63 Bis-anthracycline antibiotics inhibit human immunodeficiency virus type 1 transcription; Kutsch O et al.; The increasing numbers of human immunodeficiency virus type 1 (HIV-1) strains that exhibit resistance to antiretroviral agents used at present require the development of new effective antiretroviral compounds . Tat transactivation was recognized early on as an attractive target for drug interference . To screen for and analyze the effects of compounds that interfere with Tat transactivation, we developed several cell-based reporter systems in which enhanced green fluorescence protein is a direct and quantitative marker of HIV-1 expression or Tat-dependent long terminal repeat activity . Using these reporter cell lines, we found that the bis-anthracycline WP631, a recently developed DNA intercalator, efficiently inhibits HIV-1 expression at subcytotoxic concentrations . WP631 also abrogated acute HIV-1 replication in peripheral blood mononuclear cells infected with various primary virus isolates . We demonstrate that WP631-mediated HIV-1 inhibition is caused by the inhibition of Tat transactivation . The data presented suggest that WP631 could serve as a lead compound for a new type of HIV-1 inhibitor. Ann Allergy Asthma Immunol, 2004 Apr, 92(4), 426 - 32 Antibiotic desensitization for the allergic patient: 5 years of experience and practice; Turvey SE et al.; BACKGROUND: Antibiotic desensitization is an option for patients with suspected IgE-mediated antibiotic allergy when no other alternative exists for treating life-threatening bacterial infections . However, there are limited data describing the outcomes of this procedure with newer, commonly used antibiotics . OBJECTIVE: To evaluate the safety and utility of antibiotic desensitization . METHODS: We retrospectively reviewed the medical records of all patients undergoing antibiotic desensitization in our institution between November 1996 and November 2001 . RESULTS: There were a total of 57 desensitizations performed in 21 patients . The mean age of the patients was 22.8 years (range, 1.9-44.5 years) and 15 (71%) were female . Nineteen (90%) of the 21 patients had been diagnosed as having cystic fibrosis . In 33 (100%) of 33 desensitizations to unique antibiotics that occurred during the study period, the indication for desensitization was a history suggestive of an IgE-mediated reaction to the antibiotic and/or a positive skin test result to the antibiotic or a known cross-reactive antibiotic . Desensitizations were performed to 12 different antibiotics . Successful outcomes were achieved in 43 desensitizations (75%) . Of the 11 cases (19%) that were terminated due to an allergic reaction, there were no fatalities, intubations, or other aggressive interventions besides the use of epinephrine, antihistamines, and corticosteroids . In 7 of 11 unsuccessful desensitizations, a non-IgE mechanism appeared to be responsible for the allergic reaction . CONCLUSIONS: Antibiotic desensitization is a useful option when treating patients with life-threatening infections who must receive antibiotics to which they have an IgE-mediated allergy . These data indicate that in most cases, patients with presumed IgE-mediated antibiotic allergy may safely receive antibiotics after desensitization. Kansenshogaku Zasshi, 2004 Mar, 78(3), 241 - 7 {A pilot study of antibiotic cycling for the treatment of febrile neutropenia patients with hematological diseases}; Ikegaya S et al.; Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times . The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period . There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period . However, the efficacy rate has been rising and febrile duration has been shortening by degrees . Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling . Recently, antibiotic cycling therapy has attracted attention especially in the ICU . However, a clinical study of treatment for febrile neutropenia has not been reported . Our trial suggests that cycling therapy may be useful for febrile neutropenia . However, Some deviation in the patients characteristics of each period may affect the result . It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia. Mol Microbiol, 2004 May, 52(3), 895 - 902 Identification of the Entner-Doudoroff pathway in an antibiotic-producing actinomycete species; Gunnarsson N et al.; The metabolic network of the central carbon metabolism represents the backbone of cellular metabolism and provides the precursors and cofactors required for synthesis of secondary metabolites . It is therefore pivotal to map the operating metabolic network in the central carbon metabolism in order to design metabolic engineering strategies towards construction of more efficient producers of specific metabolites . In this context, methods that allow rapid and reliable mapping of the central carbon metabolism are valuable . In the present study, a (13)C labelling-based method was used to identify the primary metabolic pathways of the poorly characterized antibiotic-producing actinomycete Nonomuraea sp . ATCC 39727 . Surprisingly, it was found that Nonomuraea sp . ATCC 39272 predominantly metabolizes glucose via the Entner-Doudoroff (ED) pathway . This represents the first time that the ED pathway has been recognized as the main catabolic pathway in an actinomycete . The Nonomuraea genes encoding the key enzymes of the ED pathway were subsequently identified, sequenced and functionally described. Ann Pharmacother, 2004 Jun, 38(6), 928 - 35 Epub 2004 Apr 20. Trends in emergency department antibiotic prescribing for acute respiratory tract infections; Thorpe JM et al.; BACKGROUND: Injudicious use of antibiotics is associated with the reported rise in antibiotic-resistant bacteria . With an estimated 26 million antibiotics being prescribed annually in the emergency department (ED), the ED represents an important setting for targeting interventions . OBJECTIVE: To provide national estimates of potentially inappropriate antibiotic prescribing during ED visits for acute respiratory tract infections (ARTIs) and examine associations between patient, provider, visit characteristics, and antibiotic prescribing patterns . METHODS: A cross-sectional study was conducted of ED visits for ARTIs, identified from pooled 1995-2000 National Hospital Ambulatory Medical Care Survey data . National estimates, descriptive statistics, and multivariate analyses were used to assess antibiotic prescribing patterns . RESULTS: An estimated 51.3 million ED visits for ARTIs occurred during the study period, 62% of which had an antibiotic prescribed . For a narrowly defined subset of ARTIs, where antibiotic therapy is nearly always inappropriate (eg, nasopharyngitis, ARTI of multiple or unspecified sites, acute bronchitis), the percentage decreased over the 6-year period from 57% to 44% (p < 0.01) . For children ED visits, however, the downward trend occurred almost exclusively in urban EDs . Compared with visits in which a resident or intern physician was involved, the odds of antibiotic prescribing for child ED ARTI visits were 2.2 times higher for staff physicians (95% CI 1.3 to 3.6) and 1.8 times higher for nonphysicians with prescribing privileges (95% CI 1.3 to 2.4) . CONCLUSIONS: ED antibiotic prescribing for ARTIs has decreased from 1995 to 2000, but still is occurring in well over half of ED visits for ARTI . Further research assessing knowledge and attitudes of patients and providers about antibiotic prescribing is needed. Neuromuscul Disord, 2004 May, 14(5), 307 - 12 Competitive and open channel block of recombinant nAChR channels by different antibiotics; Schlesinger F et al.; Various antibiotics may impair neuromuscular transmission, provoking symptoms of myasthenia in patients with a compromised safety margin of the synaptic transmission, but little is known about the underlying mechanisms at the molecular level . Using a modified patch-clamp technique in combination with an ultrafast system for solution exchange we investigated the functional interaction of gentamicin, penicillin G, tetracycline, erythromycin and ceftriaxone with nAChR transiently transfected into HEK293 cells as a potential molecular target . Gentamicin, penicillin G, tetracycline and erythromycin induced a combination of open channel and competitive block of nAChR channel currents whereas ceftriaxone had no effect . The IC50 for the competitive block was close to or within the range of clinically relevant concentrations . Except for erythromycin the open channel block was observed only at higher concentrations . From our in-vitro results we conclude that competitive inhibition of nAChR channels by antibiotics is an important mechanism underlying the impairment of neuromuscular transmission under clinical conditions. J Drugs Dermatol, 2004 Mar-Apr, 3(2), 146 - 54 Topical retinoid and antibiotic combination therapy for acne management; Weiss JS et al.; The agents most commonly used in combination for the management of acne include topical retinoids and antibiotics . Topical retinoids normalize desquamation of the follicular epithelium, whereas antibiotics inhibit the growth of P . acnes and the production of free fatty acids . This therapeutic combination decreases comedogenesis, bacterial growth, and inflammation, thus targeting three of the four pathogenic factors associated with acne . Efficacy and tolerance are maximized with combination therapy, and the degree of skin irritation is minimized . Furthermore, adjunctive therapy with topical retinoids and antibiotics tends to produce results more quickly than single-agent therapy . This article will examine the individual agents used in combination for acne management, and discuss the mechanisms by which they achieve efficacy . The rationale of utilizing topical retinoids with antibiotics will be highlighted, particularly in relation to improved tolerance and reduced irritation. Pancreas, 2004 May, 28(4), 369 - 73 Efficacy of continuous regional arterial infusion of a protease inhibitor and antibiotic for severe acute pancreatitis in patients admitted to an intensive care unit; Imaizumi H et al.; To investigate the efficacy of continuous regional arterial infusion (CRAI) of a protease inhibitor and antibiotic for severe acute pancreatitis (SAP) in patients admitted to an intensive care unit (ICU) . A total of 51 patients with SAP requiring admission to an ICU were studied . The patients were divided into two groups: one received the protease inhibitor nafamostat mesylate and the antibiotic imipenem by continuous regional arterial infusion (CRAI group) and the other received protease inhibitors and antibiotics by intravenous infusion (non-CRAI group) . To evaluate the therapeutic usefulness of CRAI of a protease inhibitor and antibiotic for SAP, the rate of surgery and the cumulative survival rate were compared between the non-CRAI group and the CRAI group . The rate of surgery was 32% in the non-CRAI group and 9% in the CRAI group (P = 0.08) . Cumulative survival rates at 1, 6, and 12 months were 77.9%, 48.9%, and 48.9% in the non-CRAI group compared with 100.0%, 100.0%, and 87.1% in the CRAI group . Outcome was thus significantly better in the CRAI group than in the non-CRAI group (P = 0.002) . CRAI of a protease inhibitor and antibiotic may decrease the need for surgical therapy and reduce mortality in patients with SAP. Crit Care Med, 2004 Mar, 32(3), 655 - 9 Format of medical order sheet improves security of antibiotics prescription: The experience of an intensive care unit; Wasserfallen JB et al.; OBJECTIVE: To assess whether formatting the medical order sheet has an effect on the accuracy and security of antibiotics prescription . DESIGN: Prospective assessment of antibiotics prescription over time, before and after the intervention, in comparison with a control ward . SETTING: The medical and surgical intensive care unit (ICU) of a university hospital . PATIENTS: All patients hospitalized in the medical or surgical ICU between February 1 and April 30, 1997, and July 1 and August 31, 2000, for whom antibiotics were prescribed . INTERVENTION: Formatting of the medical order sheet in the surgical ICU in 1998 . MEASUREMENTS AND MAIN RESULTS: Compliance with the American Society of Hospital Pharmacists' criteria for prescription safety was measured . The proportion of safe orders increased in both units, but the increase was 4.6 times greater in the surgical ICU (66% vs . 74% in the medical ICU and 48% vs . 74% in the surgical ICU) . For unsafe orders, the proportion of ambiguous orders decreased by half in the medical ICU (9% vs . 17%) and nearly disappeared in the surgical ICU (1% vs . 30%) . The only missing criterion remaining in the surgical ICU was the drug dose unit, which could not be preformatted . The aim of antibiotics prescription (either prophylactic or therapeutic) was indicated only in 51% of the order sheets . CONCLUSIONS: Formatting of the order sheet markedly increased security of antibiotics prescription . These findings must be confirmed in other settings and with different drug classes . Formatting the medical order sheet decreases the potential for prescribing errors before full computerized prescription is available. Adv Biochem Eng Biotechnol, 2004, 86, 255 - 78 Adsorptive separation of beta-lactam antibiotics: technological perspectives; Dutta M et al.; An overview on adsorptive separation of cephalosporin antibiotics has been presented . The fundamental aspects on adsorption mechanism, kinetic and column dynamics have been exhaustedly discussed . The importance of molecular modelling studies on deducing implications for design of adsorbents has been highlighted . Finally, some aspects of process design and scale-up of adsorption column have been addressed and research needs of pragmatic importance have been identified. Water Res, 2004 Apr, 38(8), 2111 - 6 Standardized tests fail to assess the effects of antibiotics on environmental bacteria; Kummerer K et al.; Pharmaceuticals are designed and used because of their specific biological effects . Over the past decade, compounds from various classes of pharmaceuticals have been detected in the environment . Concern has grown about the adverse effects pharmaceuticals in the environment might potentially have on human and ecological health . A sound risk assessment is therefore urgently needed for pharmaceuticals . Standardized tests for assessing the effects of chemicals on environmental organisms are widely used for this purpose . However it is questionable whether classical standardized tests give reliable data needed for environmental risk assessment . In this study we investigated the suitability of the respiration inhibition test OECD 209 for the assessment of the effects of antibiotics, disinfectants and cytotoxics on sewage sludge bacteria . We found that inhibition concentrations can strongly depend on the test period and the type of compound . We conclude that tests to assess the effects of pharmaceuticals on environmental organisms such as bacteria have to be evaluated before their results can be used in environmental risk assessment. J Infus Nurs, 2004 Mar-Apr, 27(2), 118 - 22 Evidence for the use of the antibiotic lock technique; Bagnall-Reeb H; Long-term central venous catheters are essential for the treatment of patients requiring long-term intravenous medications, blood product support, and total parenteral nutrition . Thrombosis and infection, complications commonly associated with the use of these devices, represent an important cause of morbidity and mortality . To reduce the incidence of device removal because of persistent central venous catheter-related infection, the novel use of a highly concentrated antibiotic "lock" solution instilled into the catheter lumen for a defined time has been explored . This technique has been successful in numerous small uncontrolled studies, suggesting that an antibiotic lock may be effective in salvaging infected central venous access devices . Currently, the Centers for Disease Control and Prevention Guidelines on the management of central venous access device infections support the use of this technique only for patients requiring long-term access who repeatedly experience catheter-related bloodstream infections despite stringent catheter care . Additional studies are warranted to support these preliminary data. J AOAC Int, 2004 Jan-Feb, 87(1), 25 - 30 Rapid forensic selected reaction monitoring liquid chromatography/mass spectrometry determination of ionophore antibiotics found at toxic levels in animal feeds; Ebel JG et al.; A rapid, accurate, and selective method was developed for the forensic determination of ionophore antibiotics in animal feeds . A simple extraction procedure and liquid chromatography/tandem mass spectrometry (LC/MS/MS) in the selected reaction monitoring (SRM) mode were used for rapid identification and confirmation of monensin and lasalocid in feed samples and for quantitation of monensin . Extracts from a homogenous portion of ground feeds were prepared using liquid-solid extraction and liquid-liquid extraction techniques . Feed extracts were further purified by a simple defatting and solvent wash step and then concentrated to dryness . Feed extract residues were reconstituted in 1 mL LC mobile phase and a 2 microL aliquot injected into the SRM LC/MS system . The latter system used a C18, 100 x 2.0 mm, LC column coupled to a PE-Sciex API 2000 tandem triple quadrupole mass spectrometer equipped with a TurbolonSpray LC/MS interface . Feed samples were extracted and analyzed for the determination of monensin and lasalocid within a couple of hours . Control feed samples fortified with monensin at concentrations from 50 ppb to 5 ppm provided a linear response and calibration curve across this range with a correlation coefficient of 0.996. Postgrad Med J, 2004 Apr, 80(942), 196 - 200 Effect of maternal antibiotics on breast feeding infants; Mathew JL; Antibiotic usage is fairly common among breastfeeding mothers and there is potential for transfer to infants through breast milk . While most medicines taken by lactating women cause no harm to their babies, at times it can result in serious consequences . This article reviews the principles governing transfer of maternal antibiotics to breast milk, its clinical significance, and ways to minimise inadvertent infant exposure. Genome Res, 2004 May, 14(5), 893 - 900 Epub 2004 Apr 12. Systematic insertional mutagenesis of a streptomycete genome: a link between osmoadaptation and antibiotic production; Bishop A et al.; The model organism Streptomyces coelicolor represents a genus that produces a vast range of bioactive secondary metabolites . We describe a versatile procedure for systematic and comprehensive mutagenesis of the S . coelicolor genome . The high-throughput process relies on in vitro transposon mutagenesis of an ordered cosmid library; mutagenized cosmids with fully characterized insertions are then transferred by intergeneric conjugation into Streptomyces, where gene replacement is selected . The procedure can yield insertions in upward of 90% of genes, and its application to the entire genome is underway . The methodology could be applied to many other organisms that can receive DNA via RK2/RP4-mediated intergeneric conjugation . The system permits introduction of mutations into different genetic backgrounds and qualitative measurement of the expression of disrupted genes as demonstrated in the analysis of a hybrid histidine kinase and response regulator gene pair, osaAB, involved in osmoadaptation in Streptomyces . The independently transcribed response regulator gene, osaB, is essential for osmoadaptation; when grown with supplementary osmolyte, an osaB mutant cannot erect aerial hyphae and produces up to fivefold greater antibiotic yields than the wild-type strain. J Biol Chem, 2004 Jun 18, 279(25), 26518 - 25 Epub 2004 Apr 09. Polyamines affect diversely the antibiotic potency: insight gained from kinetic studies of the blasticidin S AND spiramycin interactions with functional ribosomes; Petropoulos AD et al.; The effects of spermine on peptidyltransferase inhibition by an aminohexosylcytosine nucleoside, blasticidin S, and by a macrolide, spiramycin, were investigated in a model system derived from Escherichia coli, in which a peptide bond is formed between puromycin and AcPhe-tRNA bound at the P-site of poly(U)-programmed ribosomes . Kinetics revealed that blasticidin S, after a transient phase of interference with the A-site, is slowly accommodated near to the P-site so that peptide bond is still formed but with a lower catalytic rate constant . At high concentrations of blasticidin S (>10 x K(i)), a second drug molecule binds to a weaker binding site on ribosomes, and this may account for the onset of a subsequent mixed-noncompetitive inhibition phase . Spermine enhances the blasticidin S inhibitory effect by facilitating the drug accommodation to both sites . On the other hand, spiramycin (A) was found competing with puromycin for the A-site of AcPhe-tRNA.poly(U).70 S ribosomal complex (C) via a two-step mechanism, according to which the fast formation of the encounter complex CA is followed by a slow isomerization to a tighter complex, termed C(*)A . In contrast to that observed with blasticidin S, spermine reduced spiramycin potency by decreasing the formation and stability of complex C(*)A . Polyamine effects on drug binding were more pronounced when a mixture of spermine and spermidine was used, instead of spermine alone . Our kinetic results correlate well with cross-linking and crystallographic data and suggest that polyamines bound at the vicinity of the antibiotic binding pockets modulate diversely the interaction of these drugs with ribosomes. Pharmacoepidemiol Drug Saf, 1999 Jan, 8(1), 51 - 5 Prescribing antibiotics in government health facilities in the Philippines within the context of the WHO-CARI programme; Vergeire-Dalmacion G et al.; ARI deaths at 10.23/1000 infants in the Philippines remain disturbingly 12 and 50 times higher than corresponding rates from the United States and Canada . A cross-sectional study of all government health facilities in two pre-selected areas where the WHO-CARI Program has been implemented was conducted to determine the pattern of prescribing antibiotics for ARI . The therapeutic and diagnostic guideline recommended by the WHO Program was used as a benchmark to identify irrational prescribing . Only 297 encounters out of 885 evaluable cases (35%) had their respiratory rates counted by the prescribers . There was a high proportion of undiagnosed cases at 25% and low agreement between diagnoses of prescribers and those based on the CARI guideline . Moreover, there was failure to treat cases perceived as pneumonia with antibiotics while cases perceived as simple acute respiratory infection were over-treated with the same . However, inter-observer reliability of counting respiratory rates between the research team and caregivers was fair at 0.71 . Pharmacoepidemiol Drug Saf, 1999 Jan, 8(1), 15 - 21 The association of some practice characteristics with antibiotic prescribing; Wilson RP et al.; BACKGROUND: Antibiotic prescribing in general practice is often considered inappropriate, and its volume excessive . Considerable variation in antibiotic prescribing volume and costs exists among practices . OBJECTIVE: To investigate some factors behind the variation in antibiotic prescribing among general practices, by examining the contribution to this variation of the level of deprivation in the practice population, training status, partnership status, and fundholding status . METHOD: Analysis of prescribing data (PACT) from 351 practices in the Mersey region for the year ending March 1991 and the year ending March 1994; prescribing data standardized for variation in practice population demography . Use of multiple linear regressions to investigate the variation among practices in standardized prescribing volume and standardized prescribing costs, in both years . RESULTS: Level of deprivation, training status and partnership status contributed to the models explaining variation in prescribing volume . The same variables contributed to the model explaining variation in prescribing costs in the year ending March 1991 . For the year ending March 1994, level of deprivation, training status, and fundholding status contributed to all models . CONCLUSION: Higher levels of antibiotic prescribing occur in practices serving more deprived communities, in single-handed practices, and in non-training practices . These higher levels of prescribing may be due to higher levels of morbidity, but may also reflect the organization and attitudes of these practices . Pharmacoepidemiol Drug Saf, 1999 Mar, 8(2), 95 - 104 Antibiotic prescribing for respiratory tract infections in general practice; Connolly JP et al.; OBJECTIVES: (1) To describe interpractice variation in diagnosis of respiratory infections at consultation . (2) To test the hypotheses that: (a) The decision to prescribe an antibiotic in respiratory infection is influenced by the diagnosis, the perceived certainty of diagnosis, and whether or not a consultation takes place . (b) The choice of antibiotic is influenced by the diagnosis . DESIGN: A regional survey of prescribing and associated morbidity in general practice, over a 2-week period in April 1994 . SETTING: Stratified quota sample of 22 Northern Ireland practices . RESULTS: There was wide interpractice variation in diagnosis of common respiratory infections at consultation, especially tonsillitis (5.0-157.5/1000 consultations) . Overall, different diagnoses predicted the decision to prescribe an antibiotic at different levels (coryza 42.3%, tonsillitis 84.8%), but there was wide interpractice variation in the decision to prescribe for most diagnoses . With the exception of coryza and sinusitis, the perceived certainty of diagnosis did not significantly influence the decision to prescribe . The decision to prescribe was not significantly influenced by whether or not a consultation took place . Overall, broad spectrum penicillins were the therapeutic group most frequently prescribed for a given diagnosis with the exception of tonsillitis (phenoxymethylpenicillin) and sinusitis (tetracyclines), but there was wide interpractice variation in choice of antibiotic . CONCLUSIONS: Little consensus exists among practices regarding rational prescribing decisions in respiratory illness . The absence of a consultation was no deterrent to antibiotic prescribing . At one extreme, it is suggested that some practices are avoiding consultations for respiratory infections . There is wide variation in choice of antibiotic, despite existing guidelines . Pharmacoepidemiol Drug Saf, 1999 Mar, 8(2), 81 - 94 Risk of bleeding and hypoprothrombinaemia associated with NMTT side chain antibiotics: using cefoperazone as a test case; Strom BL et al.; A retrospective cohort study was performed to determine the incidence of hypoprothrombinaemia and bleeding in patients receiving cefoperazone, a third-generation cephalosporin that contains an NMTT side chain . 374 patients receiving cefoperazone from February 1983 to March 1986 at a teaching hospital in Philadelphia were compared with 497 patients receiving either ceftizoxime or cefotaxime during the same period, and with 476 patients receiving ceftazidime from April 1985 to December 1987 . Adverse events (any bleeding episodes, decrease in haemoglobin, prolongation of prothrombin time (PT), and prolongation of partial thromboplastin times (PTT)) were evaluated, if occurring during the period from the start of cephalosporin therapy, or the start of therapy with one of the two control drugs, for 14 days after the last date of the first course of therapy were recorded . An increased risk of hypoprothrombinaemia was associated with the use of cefoperazone: the prothrombin time was prolonged by 5 s or more in 12.3% of patients receiving cefoperazone vs . 5.8% of patients receiving ceftizoxime or cefotaxime, and vs . 5.8% receiving ceftazidime; the adjusted odds ratios (95% CIs) were 3.6 (1.7-7.4) and 3.8 (1.8-7.8), respectively, and these increased at higher doses of cephalosporin . No protection was apparent from the administration of vitamin K prior to or during the course of cephalosporin . No overall increased risks were observed for bleeding (adjusted odds ratios (95% CIs) were 1.1 (0.8-1.4) vs . ceftizoxime or cefotaxime, and 0.9 (0.6-1.2) vs . ceftazidime), decrease in haemoglobin, or increased partial thromboplastin time . In subgroup analyses, increased risks of bleeding were observed with high dose cefoperazone use {2.8 (1.5-5.5) vs . ceftizoxime or cefotaxime, and 2.3 (1.1-4.6) vs . ceftazidime} . Patients receiving NMTT side chain antibiotics should be monitored for hypoprothrombinaemia, but any increase in bleeding is likely to be small, and prophylactic vitamin K is probably not warranted . Pharmacoepidemiol Drug Saf, 2004 Mar, 13(3), 181 - 5 Antibiotic use profile at paediatric clinics in two transitional countries; Palcevski G et al.; PURPOSE: In this study, we evaluated antibiotic utilisation pattern at two paediatric clinics in different European (transitional) countries: Croatia (Rijeka) and Russia (Smolensk) . METHODS: Antibiotic utilisation during the year 2000 was observed using the ATC/defined daily doses (DDD) methodology (ATC code-J01) . Drug-usage data was expressed in numbers of DDD/100 bed-days and the DU90% profile . RESULTS: In Rijeka, 35 different systemic antibiotics were used and in Smolensk 22 . The overall consumption of antibiotic drugs in Rijeka was more than three times higher than in Smolensk (28.96 vs 8.3 DDD/100 bed-days) . The top five antibiotic drugs used in Smolensk were amoxicillin, mydecamicin, ampicilin, doxycylin, gentamicin; and in Rijeka cefuroxime axetil, ceftriaxone, azytromycin, ceftibuten and amoxicillin . CONCLUSION: Differences in antibiotic prescribing patterns are greater than expected . The pattern of antibiotic utilisation in both countries implies that regional control measures and guidelines for antibiotic use in children should be urgently established. Int J Gynaecol Obstet, 2004 Mar, 84(3), 300 - 7 Prophylactic antibiotic in labor and delivery; ACOG; The use of antibiotics to prevent infections during pregnancy and the puerperium is clearly different from the use of antibiotics to treat established infections . Prophylactic antibiotics are frequently prescribed on an "empiric" basis, which for many years was thought to have few adverse consequences . Concerns about the emergence of resistant strains of common bacteria, in addition to the emergence of strains with increased virulence, have resulted in increased scrutiny of the use of antibiotics, particularly in the hospital setting . Cost considerations also affect the use and choice of prophylactic agents . The purpose of this Practice Bulletin is to present a review of clinical situations in which prophylactic antibiotics are frequently prescribed and to weigh the evidence supporting the use of antibiotics in these scenarios. Proc Natl Acad Sci U S A, 2004 Mar 30, 101(13), 4390 - 5 Epub 2004 Mar 18. Characterization of a regiospecific epivancosaminyl transferase GtfA and enzymatic reconstitution of the antibiotic chloroeremomycin; Lu W et al.; Chloroeremomycin, a vancomycin family glycopeptide antibiotic has three sugars, one D-glucose and two L-4-epi-vancosamines, attached to the crosslinked heptapeptide backbone by three glycosyltransferases, GtfA, -B, and -C . Prior efforts have revealed that GtfB and -C in tandem build an epivancosaminyl-1,2-glucosyldisaccharide chain on residue 4 of the aglycone; however, the characterization of GtfA and glycosylation sequence of chloroeremomycin have been lacking . Here, we report the expression and purification of GtfA, as well as synthesis of its sugar donor, 2'-deoxy-thymidine 5'-diphosphate (dTDP)-beta-L-4-epi-vancosamine . GtfA transfers 4-epi-vancosamine from the chemically synthesized dTDP-4-epi-vancosamine to the beta-OH-Tyr6 residue of the aglycone, preferentially after GtfB action, to generate chloroorienticin B . With the preferred kinetic order of GtfB, then GtfA, then GtfC established, we have succeeded in reconstitution of chloroeremomycin from the heptapeptide aglycone by the sequential actions of the three enzymes. Jpn J Clin Oncol, 2004 Feb, 34(2), 69 - 73 Randomized trial of oral versus intravenous antibiotics in low-risk febrile neutropenic patients with lung cancer; Niho S et al.; BACKGROUND: Neutropenic fever is one of the most serious adverse effects of cancer chemotherapy . Neutropenia may cause a life-threatening bacterial infection . Therefore, febrile neutropenic inpatients are empirically treated with intravenous broad-spectrum antibiotics . Recently, several studies have suggested the presence of low-risk groups among febrile neutropenic patients . METHODS: A prospective randomized trial was conducted to compare treatment with oral ciprofloxacin (200 mg) and amoxicillin-clavulanate (375 mg) administered every 8 h against that with intravenous ceftazidime (1 g) administered every 12 h in low-risk febrile neutropenic patients with lung cancer . All patients received chemotherapy and antibiotic therapy while being hospitalized . RESULTS: A total of 177 patients with lung cancer agreed to participate in this study prior to undergoing chemotherapy . Among them, a total of 36 neutropenic patients with 42 febrile episodes were enrolled in the study . Treatment was successful without the need for modification in 91% of the episodes in patients receiving the oral regimen and 79% of the episodes in patients receiving the intravenous regimen . No treatment-related deaths occurred . One patient developed nausea while receiving the oral regimen, so the oral regimen was changed to the intravenous regimen in this patient . CONCLUSIONS: This prospective study suggested that treatment with oral antibiotics ciplofloxacin plus amoxicillin-clavulanate was effective for low-risk febrile neutropenic patients after chemotherapy. Appl Environ Microbiol, 2004 Apr, 70(4), 2560 - 5 Antibiotic production by a Roseobacter clade-affiliated species from the German Wadden Sea and its antagonistic effects on indigenous isolates; Brinkhoff T et al.; A strain affiliated with the Roseobacter clade and producing a new antibiotic named tropodithietic acid (L . Liang, Ph.D . thesis, University of Gottingen, Gottingen, Germany, 2003) was isolated from the German Wadden Sea . The compound showed strong inhibiting properties with respect to marine bacteria of various taxa and marine algae . Antibiotic production was found to occur during the complete growth phase . Strain mutants without antagonistic properties appeared several times spontaneously. J Pediatr Surg, 2004 Apr, 39(4), 634 - 6 D-lactic acidosis in short-bowel syndrome managed with antibiotics and probiotics; Uchida H et al.; D-lactic acidosis sometimes occurs in malabsorbed patients with short-bowel syndrome and is characterized by recurrent episodes of encephalopathy and metabolic acidosis . The characteristic neurologic abnormalities and the presence of metabolic acidosis raises a diagnostic suspicion, and the diagnosis is made when the serum level of D-lactic acid is greater than 3 mmol/L . Standard treatment consists of restricting oral carbohydrates or fasting, correction of metabolic acidosis, and a long-term suppression of pathogenic floras with antibiotics . The authors present a case of D-lactic acidosis in a 22-year-old patient with short-bowel syndrome, to whom intestinal bacterial agents (probiotics) were given in addition to oral kanamycin . Recolonization of the intestine with nonpathogenic floras should be a long-term treatment for D-lactic acidosis. Scand J Infect Dis, 2004, 36(2), 139 - 43 Data from electronic patient records are suitable for surveillance of antibiotic prescriptions for respiratory tract infections in primary health care; Engstrom S et al.; Diagnoses and antibiotic treatments were analysed in relation to respiratory tract infections (RTI) . A 1-y retrospective study was made of electronic patient records (EPR) for encounters concerning RTIs in primary health care in Sweden . The study covered a registered population of 102,050 individuals at 12 primary health care centres in 3 counties . Data were recorded on number of episodes, encounters, diagnostic codes and antibiotic prescriptions . The yearly number of episodes of RTIs was 16,964 or 166 per 1000 inhabitants per y . The total number of encounters was 19,965 . The most frequent diagnoses were common cold (40%), acute tonsillitis (18%), and acute bronchitis (15%) . The yearly number of antibiotic prescriptions was 7961, accounting for 47% of the episodes or 78 per 1000 inhabitants per y . The most frequently prescribed antibiotics were phenoxymethylpenicillin (61%), tetracyclines (18%) and macrolides 8%) . Standard EPRs provide a feasible source of clinical information which, taking limitations into consideration, could be used for the follow-up of trends in antibiotic prescribing and of adherence to guidelines with regard to RTIs. Tex Heart Inst J, 2004, 31(1), 33 - 8 Antibiotic trials for coronary heart disease; Anderson JL et al.; The possibility has been raised in recent years that infection might contribute as an inflammatory stimulus to chronic "noninfectious" degenerative diseases . Within the past decade, serious attention has been given to the possibility of bacterial vectors as causal factors of atherosclerosis . To date, the greatest amount of information has related to the intracellular organism Chlamydia pneumoniae . This interest has been stimulated by the frequent finding of bacterial antigens and, occasionally, recoverable organisms, within human atherosclerotic plaque . Indirect evidence for and against the benefit of anti-Chlamydia antibiotic agents comes from epidemiologic studies . Given the potential for confounding in observational studies, prospective, randomized intervention trials are required . These antibiotic trials have generated enthusiastic expectations for proving (or disproving) the infectious-disease hypothesis of atherosclerosis and establishing new therapies . However, these expectations have been tempered by important limitations and uncertainties . Negative outcomes can be explained not only by an incorrect hypothesis but also by inadequate study size or design or by an ineffective antibiotic regimen . In contrast, if studies are positive, the hypothesis still is not entirely proved, because a nonspecific anti-inflammatory effect or an anti-infective action against other organisms might be operative . The clinical trial data to date have not provided adequate support for the clinical use of antibiotics in primary or secondary prevention of coronary heart disease . New and innovative experimental approaches, in addition to traditionally designed antibiotic trials, should be welcome in our attempts to gain adequate insight into the role of infection in atherosclerosis and its therapy. Eur J Gen Pract, 2004 Mar, 10(1), 18 - 23 Did local enhancement of a national campaign to reduce high antibiotic prescribing affect public attitudes and prescribing rates? Parsons S, Morrow S, Underwood M. OBJECTIVES: Due to concerns about both costs and drug resistance, reducing antibiotic prescribing is a strategic aim for the UK National Health Service . A nationwide public education campaign launched in October 1999 (CATNAP) addressed this . The objectives were 1) to assess public attitudes to antibiotic use in a district with high antibiotic prescribing where a nationwide public education campaign was locally enhanced; 2) to assess the impact of the campaign on prescribing of antibiotics locally . DESIGN: 1) Questionnaire survey to test the hypothesis that public attitudes would be equivalent before and after local enhancement of the national campaign . 2) Prescribing data analysis to assess the impact of the campaign on prescribing of antibiotics . SETTING: London borough of Barking and Dagenham . OUTCOME MEASURES: 1) Differences in public attitudes to antibiotic prescribing pre and post the locally enhanced campaign . 2) Changes in prescribing rates pre and post the locally enhanced campaign . RESULTS: 1) Response rates in questionnaire study: 45% (442/982) initially, 42% (815/1941) at follow-up . Responses to all general questions were equivalent in both surveys . There was considerable misunderstanding amongst the population about the effectiveness of antibiotics, particularly in relation to viral infections, colds, sore throats and coughs . The proportion of responders who believed that children should be prescribed antibiotics for a fever was not equivalent in the two surveys, it decreased from 56% to 49%, the limit of the one-sided confidence interval was 13.5% . 2) The rate of change in prescriptions dispensed between 1998/9 and 1999/2000 was not significantly different from that expected, based on the previous years, in either England and Wales or Barking and Dagenham . CONCLUSION: Using this study design and this method of locally enhancing a public education campaign, the locally enhanced campaign did not appear to influence the public's attitudes towards antibiotic prescribing in an area of high prescribing . Assessment of the attitudes of those who had definitely been exposed to the campaign and its messages to, and by, GPs might be more likely to produce a demonstrable change in attitudes. J Foot Ankle Surg, 2004 Mar-Apr, 43(2), 97 - 103 The efficacy of prophylactic intravenous antibiotics in elective foot and ankle surgery; Zgonis T et al.; A retrospective chart review of 555 patients who received elective foot and ankle surgeries between 1995 and 2001 at 1 outpatient podiatric hospital clinic was performed to evaluate the efficacy of preoperative intravenous antibiotic use . Only those patients who were having elective foot or ankle surgery for the first time, were being followed up at the hospital's outpatient clinic, and had a nontraumatic cause for their surgery were included in this study . A wound was considered infected when purulent material from the wound sites was noted and an organism(s) was cultured . A wound complication was defined as a superficial dehiscence, edema, erythema, or stitch abscess . Three hundred six (55.1%) patients received a preoperative antibiotic and 249 (44.9%) patients did not . Of the 306 patients who received a preoperative antibiotic, 9 (1.6%) acquired a postoperative wound infection, whereas 8 (1.4%) of the 249 patients who did not receive preoperative antibiotics acquired a postoperative infection . A logistic regression model and chi square tests of association were used to determine if preoperative antibiotic use, age, gender, type of surgical procedure, operative time, tourniquet use, past medical history, and internal fixation were predictive of or associated with postoperative wound infection or complication . None of the study factors was predictive of postoperative wound infection or complication (P >.01) . Preoperative antibiotic use was associated with surgical category and internal fixation use (P <.001) but not postoperative wound infection or complication (P >.01) . The results suggest that prophylactic intravenous antibiotic use in routine elective foot and ankle surgery is not warranted. Arch Microbiol, 2004 May, 181(5), 384 - 9 Epub 2004 Mar 31. Differential production of two antibiotics of Streptomyces coelicolor A3(2), actinorhodin and undecylprodigiosin, upon salt stress conditions; Sevcikova B et al.; Production of two pigmented antibiotics, actinorhodin and undecylprodigiosin, is differentially affected in Streptomyces coelicolor A3(2) at high salt concentration, with actinorhodin being inhibited and undecylprodigiosin activated . Analysis of expression of two genes coding for pathway-specific transcriptional regulators of actinorhodin and undecylprodigiosin synthesis, actII-ORF4 and redD, revealed that their expression is similarly differentially affected . Thus, the effect of high salt concentration on actinorhodin and undecylprodigiosin production is mediated at the transcriptional level by the differential expression of genes encoding corresponding pathway-specific transcriptional regulators. Otolaryngol Head Neck Surg, 2004 Mar, 130(3 Suppl), S57 - 78 Animal ototoxicity of topical antibiotics and the relevance to clinical treatment of human subjects; Roland PS et al.; OBJECTIVE: The objective of this study was to systematically review the literature on animal ototoxicity from ototopical medications . A secondary objective was to assess the relevance of animal data to the use of ototopical drops in clinical situations involving humans . STUDY DESIGN: We performed a MEDLINE search of the published literature using appropriate search terms to identify pertinent articles, which were reviewed, summarized, and tabulated . RESULTS: One hundred seventy-three articles were reviewed; 61 articles were appropriate to the study question and were further analyzed . CONCLUSIONS: Virtually all studies demonstrate that aminoglycoside antibiotics, when applied topically into the middle ear space, are ototoxic in experimental animals. Rapid Commun Mass Spectrom, 2004, 18(6), 685 - 700 Collision-activated cleavage of a peptide/antibiotic disulfide linkage: possible evidence for intramolecular disulfide bond rearrangement upon collisional activation; Fagerquist CK; Ceftiofur is an important veterinary beta-lactam antibiotic whose bioactive metabolite, desfuroylceftiofur, has a free thiol group . Desfuroylceftiofur (DFC) was reacted with two peptides, {Arg8}-vasopressin and reduced glutathione, both of which have cysteine residues to form disulfide-linked peptide/antibiotic complexes . The products of the reaction, {vasopressin + (DFC-H) + (DFC-H) + H}+, {(vasopressin+H) + (DFC-H) + H}+ and {(glutathione-H) + (DFC-H) + H}+, were analyzed using collision-activated dissociation (CAD) with a quadrupole ion trap tandem mass spectrometer . MS/MS of {vasopressin + (DFC-H) + (DFC-H) + H}+ resulted in facile dissociative loss of one and two covalently bound DFC moieties . Loss of one DFC resulted from either homolytic or heterolytic dissociation of the peptide/antibiotic disulfide bond with equal or unequal partitioning of the two sulfur atoms between the fragment ion and neutral loss . Hydrogen migration preceded heterolytic dissociation . Loss of two DFC moieties from {vasopressin + (DFC-H) + (DFC-H) + H}+ appears to result from collision-activated intramolecular disulfide bond rearrangement (IDBR) to produce cyclic {vasopressin + H}+ (at m/z 1084) as well as other cyclic fragment ions at m/z 1084 +/- 32 and +64 . The cyclic structure of these ions could only be inferred as MS/MS may result in rearrangement to non-cyclic structures prior to dissociative loss . IDBR was also detected from MS(3) experiments of {vasopressin + (DFC-H) + (DFC-H) + H}+ fragment ions . MS/MS of {(glutathione-H) + (DFC-H) + H}+ resulted in cleavage of the peptide backbone with retention of the DFC moiety as well as heterolytic cleavage of the peptide/antibiotic disulfide bond to produce the fragment ion: {(DFC-2H) + H}+ . These results demonstrate the facile dissociative loss by CAD of DFC moieties covalently attached to peptides through disulfide bonds . Published in 2004 by John Wiley & Sons, Ltd. Antimicrob Agents Chemother, 2004 Apr, 48(4), 1402 - 5 First-choice antibiotics at subinhibitory concentrations induce persistence of Chlamydia pneumoniae; Gieffers J et al.; Persistent growth forms of Chlamydia pneumoniae have been associated with chronic infections in vivo . We investigated the effects of first-line therapeutics on the induction of persistence by monitoring recoverable organisms, gene expression of membrane proteins, and morphology . We found that all of the antibiotics tested have distinct and subinhibitory concentrations at which they induce persistence. Syst Appl Microbiol, 2004 Mar, 27(2), 160 - 5 Kribbella antibiotica sp . nov., a novel nocardioform actinomycete strain isolated from soil in Yunnan, China; Li WJ et al.; A novel nocardioform actinomycete strain YIM 31530T was isolated from a soil in Yunnan, China . Based on the results of phenotypic characteristics, phylogenetic studies and DNA-DNA hybridization results, strain YIM 31530T should be assigned to a new species of the genus Kribbella, for which the name Kribbella antibiotica sp . nov . is proposed . The type strain is YIM 31530T(= CCTCC AA001021T = DSM 15501T) . The GenBank accession number for the sequence reported in this paper is AY082063. Int Orthop, 2004 Jun, 28(3), 129 - 33 Epub 2004 Mar 23. Antibiotic-loaded bone cement spacers in two-stage management of infected total knee arthroplasty; Pitto RP et al.; We reviewed the current use of spacers in the management of the infected knee prosthesis . There are two types of temporary spacers: block or non-articulating spacers and articulating or mobile spacers . Generally, spacers improve mobilisation and hasten recovery with shorter hospital stay between stages . Furthermore, spacers facilitate the second-stage procedure by maintaining joint space, and articulating spacers may also maintain range of motion . Last but not the least, the cost of spacers represents only a small fraction of the total expenses for management of infected knee arthroplasties. West Indian Med J, 2003 Dec, 52(4), 317 - 20 Routine prophylactic antibiotics for arthroplasty patients receiving dental care . Is it necessary? Rose RE. Much of the debate regarding the prophylactic use of antibiotics for patients who have had a total joint replacement has focussed on their use before dental procedures . Despite the fact that almost all orthopaedic surgeons routinely recommend antibiotics for patients with prosthetic joints who require dental treatment, there is little evidence of a definitive link between transient bacteraemia occurring during dental procedures and late infections around prosthetic joints . An extensive review of the literature reveals that most authors recommend prophylactic antibiotics in high-risk patients or in those who undergo extensive dental surgery. Biomed Chromatogr, 2004 Mar, 18(2), 86 - 9 Liquid chromatography-tandem mass spectrometry for the determination of a new oxazolidinone antibiotic DA-7867 in human plasma; Ji HY et al.; A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the determination of a new ox-azolidinone antibiotic DA-7867, (S)-{N-3-(4-(2-(1-methyl-5-tetrazolyl)-pyridine-5-yl)-3- fl uorophenyl)-2-oxo-5-oxazolidinyl}methyl acetamide, in human plasma was developed . DA-7867 and internal standard, linezolid, were extracted from human plasma with ethyl acetate at acidic pH . A reverse-phase LC separation was performed on Luna C(8) column with the mixture of acetonitrile-ammonium formate (10 mm, pH 4.5; 35:65, v/v) as mobile phase . The analytes were determined using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode . The lower limits of quanti fi cation for DA-7867 was 2.5 ng/mL . The single liquid-liquid extraction quantitatively recovered DA-7867 and internal standard from plasma samples at the ranges of 82.2-86.7% . DA-7867 was stable in blank human plasma at room temperature for 24 h and following three freeze-thaw cycles . J Am Chem Soc, 2004 Mar 31, 126(12), 3837 - 44 Further studies on the biosynthesis of the manumycin-type antibiotic, asukamycin, and the chemical synthesis of protoasukamycin; Hu Y et al.; Asukamycin (2), a metabolite of Streptomyces nodosus ssp . asukaensis ATCC 29757 and a member of the manumycin family of