EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 28 2009
Anmol Kumar Ray
Abstract A total synthesis of the natural product triostin A, wherein the N -methylated depsipeptide scaffold is constructed by solution-phase peptide chemistry followed by disulfide formation and macrocyclization, is described. Finally, the quinoxalines were attached to provide the DNA bisintercalator. Analogs of triostin A were obtained by the successive functionalization of the cyclic depsipeptide with pyrimidine or purine recognition units. The attachment of functional units was achieved by the orthogonal protection of the respective side chain amino functionalities. The nucleobase-functionalized triostin analogs have the potential to recognize double-stranded DNA by hydrogen bonding. The interaction with DNA was investigated by UV spectroscopy and fluorescence intercalator displacement. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Synthesis of the Antibiotic (R)-Reutericyclin via Dieckmann Condensation

HELVETICA CHIMICA ACTA, Issue 11 2005
Roswitha Böhme
(R)-Reutericyclin ((R)- 1), a bactericidal, amphiphilic natural product with a trisubstituted tetramic acid moiety, was prepared in four steps from D -leucine in an overall yield of 24%. The chiral heterocyclic portion of 1 was synthesized by Dieckmann cyclization of ethyl N -(acetoacetyl)leucinate (7), and the resulting pyrrole derivative 8 was N -acylated with (E)-dec-2-enoyl chloride in the presence of BuLi at ,,70° (Scheme,2). This new procedure is straightforward and allows the synthesis of both antipodes of reutericyclin in an enantiomeric excess (ee) of ca. 80%. [source]

Effect of an Educational Intervention on Optimizing Antibiotic Prescribing in Long-Term Care Facilities

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2007
(See Editorial Comments by Dr. Lona Mody on pp 130, 1302)
OBJECTIVE: To assess the effect of an educational intervention aimed at optimizing antibiotic prescribing in long-term care (LTC) facilities. DESIGN: Cluster randomized, controlled trial. SETTING: Eight public LTC facilities in the Montreal area. PARTICIPANTS: Thirty-six physicians. INTERVENTION: The educational intervention consisted of mailing an antibiotic guide to physicians along with their antibiotic prescribing profile covering the previous 3 months. Targeted infections were urinary tract, lower respiratory tract, skin and soft tissues, and septicemia of unknown origin. In the prescribing profile, each antibiotic was classified as adherent or nonadherent to the guide. Physicians in the experimental group received the intervention twice, 4 months apart, whereas physicians in the control group provided usual care. MEASUREMENTS: Data on antibiotic prescriptions were collected over four 3-month periods: preintervention, postintervention I, postintervention II, and follow-up. A generalized estimating equation (GEE) model was used to compare the proportion of nonadherent antibiotic prescriptions of the experimental and control groups. RESULTS: By the end of the study, nonadherent antibiotic prescriptions decreased by 20.5% in the experimental group, compared with 5.1% in the control group. Based on the GEE model, during postintervention II, physicians in the experimental group were 64% less likely to prescribe nonadherent antibiotics than those in the control group (odds ratio=0.36, 95% confidence interval=0.18,0.73). CONCLUSION: An educational intervention combining an antibiotic guide and a prescribing profile was effective in decreasing nonadherent antibiotic prescriptions. Repetition of the intervention at regular intervals may be necessary to maintain its effectiveness. [source]

Antibiotic and Biocide Resistance in Bacteria: perceptions and realities for the prevention and treatment of infection

JOURNAL OF APPLIED MICROBIOLOGY, Issue 2002
J.-Y. Maillard
[source]

Management of children with otitis media: A survey of Australian Aboriginal Medical Service practitioners

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 7-8 2009
Hasantha Gunasekera
Aim: To determine whether Australian Aboriginal Medical Service (AMS) practitioners treat otitis media (OM) more aggressively in Aboriginal than non-Aboriginal children and the factors influencing their management decisions. Methods: A case vignette questionnaire was sent to all AMS practitioners working in December 2006. We compared responses based on the child's Aboriginal status using ,2 analysis. Results: Questionnaires were returned from 63/87 (72%) of the AMSs by 131/238 (55%) eligible practitioners. Few practitioners (13%) reported using tympanometry or pneumatic otoscopy (9%) when examining children's ears. Practitioners were more likely to treat acute OM with antibiotics (92% vs. 49%, P < 0.01) and to treat with courses longer than 7 days (25% vs. 14%, P= 0.03) in Aboriginal than non-Aboriginal children. Most practitioners (60%) used oral antibiotics to treat chronic suppurative OM and OM with effusion in Aboriginal children (58%). Factors increasing the likelihood of antibiotic use included: the child being Aboriginal (67%), wet perforations (62%) and bulging eardrums (59%). No AMS or practitioner characteristics were significant predictors. Most practitioners (99%) were aware of Therapeutic Guidelines (Antibiotic). Only half (54%) were aware of the Australian Government guidelines for managing OM in Aboriginal and Torres Strait Islander populations and only 22% used them ,often' or ,always'. Conclusions: Australian AMS practitioners treat OM more aggressively in Aboriginal children, consistent with the Australian Government guidelines, despite half being unaware of them. Opportunities to improve management include increased use of pneumatic otoscopy and tympanometry, and decreased antibiotic usage for OM with effusion and chronic suppurative OM. [source]

Primary Photophysical Properties of Moxifloxacin, A Fluoroquinolone Antibiotic

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2008
Fernando Lorenzo
The photophysical properties of the fluoroquinolone antibiotic moxifloxacin (MOX) were investigated in aqueous media. MOX in water, at pH 7.4, shows two intense absorption bands at 287 and 338 nm (, = 44 000 and 17 000 dm3 mol,1 cm,1, respectively). The absorption and emission properties of MOX are pH-dependent, pKa values for the protonation equilibria of both the ground (6.1 and 9.6) and excited singlet states (6.8 and 9.1) of MOX were determined spectroscopically. MOX fluoresces weakly, the quantum yield for fluorescence emission being maximum (0.07) at pH 8. Phosphorescence from the excited triplet state in frozen ethanol solution has a quantum yield of 0.046. Laser flash photolysis and pulse radiolysis studies have been carried out to characterize the transient species of MOX in aqueous solution. On laser excitation, MOX undergoes monophotonic photoionization with a quantum yield of 0.14. This leads to the formation of a long-lived cation radical whose absorption is maximum at 470 nm (,470 = 3400 dm3 mol,1 cm,1). The photoionization process releases hydrated electron which rapidly reacts (k = 2.8 × 1010 dm3 mol,1 s,1) with ground state MOX, yielding a long-lived anion radical with maximum absorption at 390 nm (,390 = 2400 dm3 mol,1 cm,1). The cation radical of MOX is able to oxidize protein components tryptophan and tyrosine. The bimolecular rate constants for these reactions are 2.3 × 108 dm3 mol,1 s,1 and 1.3 × 108 dm3 mol,1 s,1, respectively. Singlet oxygen sensitized by the MOX triplet state was also detected only in oxygen-saturated D2O solutions, with a quantum yield of 0.075. [source]

Closthioamide: An Unprecedented Polythioamide Antibiotic from the Strictly Anaerobic Bacterium Clostridium cellulolyticum,

ANGEWANDTE CHEMIE, Issue 11 2010
Thorger Lincke Dipl.-Chem.
Schwefel für die sauerstofffreie Welt: Closthioamid (1), der einzige bekannte sekundäre Metabolit eines streng anaeroben Bakteriums, wurde aus anaerobem Clostridium cellulolyticum (siehe SEM-Bild) nach Induktion der Biosynthese mit einem wässrigen Bodenextrakt isoliert. Dieser neue Typ eines symmetrischen Naturstoffs, in dem alle Bausteine durch Thioamideinheiten verknüpft sind, hemmt das Wachstum multiresistenter Staphylokokken. [source]

JETACAR Antibiotic use recommendations

AUSTRALIAN VETERINARY JOURNAL, Issue 5 2005
Dr Tom Grimes
No abstract is available for this article. [source]

Conformational Transition in the Aminoacyl t-RNA Site of the Bacterial Ribosome both in the Presence and Absence of an Aminoglycoside Antibiotic

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2007
Samy O. Meroueh
Peptide bonds are made at the ribosomal decoding site. Structural information reveals that two bases in the RNA that constitute the decoding site, A1492 and A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside antibiotics bind to the decoding site, and the structural information reveals the two bases in the extrahelical positions. We have shown by explicit-solvent molecular dynamics simulations and free-energy calculations that ribosomal RNA bases A1492 and A1493 are inherently prone to sampling conformational states that include both intrahelical and extrahelical positions. The simulations reveal that base flipping occurs through the minor groove of the double helix. Furthermore, free-energy calculations for the conformational change of the bases to the extrahelical positions in both processes are exergonic and highly favorable. It is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests the bases in extrahelical conformations in the course of normal translation. In contrast, the sequestration of the aminoglycoside antibiotic at the decoding site facilitates the conformational change of the bases to the extrahelical position. Once the antibiotic is bound, the extrahelical positions for the bases are highly favored based on contributions by both electrostatic and entropic components of the free energy for the process. [source]

A Novel Fluorinated Erythromycin Antibiotic.

CHEMINFORM, Issue 52 2005
Rebecca J. M. Goss
No abstract is available for this article. [source]

Synthesis of Functionalized Cyclopentane for Pactamycin (II), a Potent Antitumor Antibiotic.

CHEMINFORM, Issue 30 2005
Takashi Tsujimoto
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

Convenient Synthesis of the Main Tridehydropentapeptide Skeleton for Macrocyclic Antibiotic, Sulfomycin I.

CHEMINFORM, Issue 16 2004
Tetsuya Kayano
No abstract is available for this article. [source]

Solid-Phase Synthesis of Dihydrovirginiamycin S1, a Streptogramin B Antibiotic

CHEMISTRY - A EUROPEAN JOURNAL, Issue 17 2004
Alex Shaginian
Abstract We describe the first solid-phase synthesis of dihydrovirginiamycin S1, a member of the streptogramin B family of antibiotics, which are nonribosomal-peptide natural products produced by Streptomyces. These compounds, along with the synergistic group A components, are "last line of defense" antimicrobial agents for the treatment of life-threatening infections such as vancomycin-resistant enterococci. The synthesis features an on-resin cyclization and is designed to allow production of streptogramin B analogues with diversification at positions 1,, 1, 2, 3, 4, and 6. Several synthetic challenges known to hinder the synthesis of this class of compounds were solved, including sensitivity to acids and bases, and epimerization and rearrangements, through the judicious choice of deprotection conditions, coupling conditions, and synthetic strategy. This work should enable a better understanding of structure,activity relationships in the streptogramin B compounds, possible identification of analogues that bypass known resistance mechanisms, and perhaps the identification of analogues with novel biological activities. [source]

Declining Antibiotic Prescriptions for Upper Respiratory Infections, 1993,2004

ACADEMIC EMERGENCY MEDICINE, Issue 4 2007
Stefan G. Vanderweil BA
Abstract Objectives: To examine antibiotic prescribing trends for U.S. emergency department (ED) visits with upper respiratory tract infections (URIs) between 1993 and 2004. Methods: Data were compiled from the National Hospital Ambulatory Medical Care Survey (NHAMCS). URI visits were identified by using ICD-9-CM code 465.9, whereas antibiotics were identified using the National Drug Code Directory class Antimicrobials. A multivariate logistic regression model revealed sociodemographic and geographic factors that were independently associated with receipt of an antibiotic prescription for URIs. Results: There were approximately 23.4 million ED visits diagnosed as URIs between 1993 and 2004. Although the proportion of URI diagnoses remained relatively stable (p trend = 0.26), a significant decrease in provision of antibiotic prescriptions for URIs occurred during this 12-year period, from a maximum of 55% in 1993, to a minimum of 35% in 2004. Patients who were prescribed antibiotics were more likely to be white than African American and to have been treated in EDs located in the southern United States. Conclusions: Antibiotic prescribing for URIs continues to decrease, a favorable trend that suggests that national efforts to reduce inappropriate antibiotic usage are having some success. Nevertheless, the frequency of antibiotic treatment for URI in the ED remains high (35%). Future efforts to reduce inappropriate antibiotic prescribing may focus on patients and physicians in southern U.S. EDs. Additional work is needed to address continued evidence of race-related disparities in care. [source]

Antibiotic Prophylaxis Guideline Awareness and Antibiotic Prophylaxis Use Among New York State Dermatologic Surgeons

DERMATOLOGIC SURGERY, Issue 9 2002
Noah Scheinfeld JD
background. Use of antibiotic prophylaxis in dermatologic surgery patients remains controversial and several sets of guidelines exist. objective. We investigated dermatologic surgeon's awareness of the American Heart Association (AHA) 1997 antibiotic prophylaxis guidelines, their use of prophylactic antibiotics, and their practices as compared with the Haas and Grekin's 1995 antibiotic prophylaxis guidelines. methods. We mailed postage-paid questionnaires regarding AHA guideline awareness and antibiotic prophylaxis use to the 235 New York State members of the American Society for Dermatologic Surgery (ASDS). We received 87 replies. results. Most participants recognize AHA guidelines and claim to follow them. We reiterate previous studies' findings. Most dermatologic surgeons use antibiotics appropriately. However, antibiotics are occasionally overused or dosed outside the guidelines. Many participants prescribe antibiotics based on a patient's other physicians' recommendations. Notably, erythromycin is sometimes used, an antibiotic the AHA no longer recommends. conclusion. Dermatologic surgeons commonly use antibiotic prophylaxis to prevent bacterial endocarditis. Based on previous studies, though, the risk of endocarditis following cutaneous surgery is low and thus the use of antibiotic prophylaxis is controversial. Although this practice is appropriate for high-risk patients when skin is contaminated, it is not recommended for noneroded, noninfected skin. We report that dermatologists may be aware of the guidelines, but only seem to partially follow them. Further studies are still needed to establish optimal guidelines. [source]

The use of systemic antibiotics in the treatment of chronic wounds

DERMATOLOGIC THERAPY, Issue 6 2006
Robert Hernandez
ABSTRACT:, The role of microorganisms in the etiology and persistence of chronic wounds remains poorly understood. The chronic wound bed houses a complex microenvironment that typically includes more than one bacterial species. Difficulty lies in determining when the presence of bacteria impedes wound healing, thereby warranting intervention. Indications for antibiotic therapy and optimal treatment regimens are ill defined. The goal of this article is to describe the appropriate role of systemic antibiotics in the management of chronic wounds. A common sense approach will be offered based on six clinically pertinent questions: ,,Is infection present? ,,Are systemic antibiotics necessary? ,,Should treatment be enteral or parenteral? ,,What antibiotic or combination of antibiotics should be used? ,,What should be the duration of therapy? ,,What special circumstances are present (i.e., concomitant illnesses, potential drug,drug interactions) that can impact therapy? [source]

Profiles in Patient Safety: Antibiotic Timing in Pneumonia and Pay-for-performance

ACADEMIC EMERGENCY MEDICINE, Issue 7 2006
Jesse M. Pines MD
The delivery of antibiotics within four hours of hospital arrival for patients who are admitted with pneumonia, as mandated by the Joint Commission for the Accreditation of Healthcare Organizations and the Centers for Medicare and Medicaid Services, has gained considerable attention recently because of the plan to implement pay-for-performance for adherence to this standard. Although early antibiotic administration has been associated with improved survival for patients with pneumonia in two large retrospective studies, the effect on actual patient care and outcomes for patients with pneumonia and other emergency department patients of providing financial incentives and disincentives to hospitals for performance on this measure currently is unknown. This article provides an in-depth case-based description of the evidence behind antibiotic timing in pneumonia, discusses potential program effects, and analyzes how the practical implementation of pay-for-performance for pneumonia conforms to American Medical Association guidelines on pay-for-performance. [source]

Diagnosing and treating diabetic foot infections

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2004
Benjamin A. Lipsky
Abstract Foot infections are a common, complex and costly complication of diabetes. We have made considerable progress in establishing consensus definitions for defining infection. Similarly, we have learned much about the appropriate ways to diagnose both soft tissue and bone infections. Accompanying these advances have been improvements in our knowledge of the proper approaches to antibiotic (and surgical) therapy for diabetic foot infections. Furthermore, investigators have explored the value of various adjunctive therapies, especially granulocyte colony stimulating factors and hyperbaric oxygen, for improving outcomes. This paper presents a summary of a minisymposium on infection of the diabetic foot that was held at the fourth International Symposium on the Diabetic Foot, in Noordwijkerhout, The Netherlands. Crown copyright 2004. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd. [source]

Simultaneous determination of metronidazole and spiramycin in bulk powder and in tablets using different spectrophotometric techniques

DRUG TESTING AND ANALYSIS, Issue 1 2010
Fatma I. Khattab
Abstract Metronidazole (MZ) is an anti-infective drug used in the treatment of anaerobic bacterial and protozoa infections in humans. It is also used as a vetinary antiparasitic drug. Spiramycin (SP) is a medium-spectrum antibiotic with high effectiveness against Gram-positive bacteria. Three simple, sensitive, selective and precise spectrophotometric methods were developed and validated for the simultaneous determination of MZ and SP in their pure form and in pharmaceutical formulations. In methods A and B, MZ was determined by the application of direct spectrophotometry and by measuring its zero-order (D0) absorption spectra at its ,max = 311 nm. In method A, SP was determined by the application of first derivative spectrophotometry (D1) and by measuring the amplitude at 218.3 nm. In method B, the first derivative of the ratio spectra (DD1) was applied, and SP was determined by measuring the peak amplitude at 245.6 nm. Method C entailed mean centring of the ratio spectra (MCR), which allows the determination of both MZ and SP. The methods developed were used for the determination of MZ and SP over a concentration range of 5,25 µg ml,1. The proposed methods were used to determine both drugs in their pure, powdered forms with mean percentage recoveries of 100.16 ± 0.73 for MZ in methods A and B, 101.10 ± 0.90 in method C, 100.09 ± 0.70, 100.02 ± 0.88 and 100.49 ± 1.26 for SP in methods A, B and C, respectively. The proposed methods were proved using laboratory-prepared mixtures of the two drugs and were successfully applied to the analysis of MZ and SP in tablet formulation without any interference from each other or from the excipients. The results obtained by applying the proposed methods were compared statistically with a reported HPLC method and no significant difference was observed between these methods regarding both accuracy and precision. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Bacteria divert resources from growth for magellanic penguin chicks

ECOLOGY LETTERS, Issue 6 2002
Jaime Potti
Abstract The influence of bacteria on the growth of their wild avian hosts is unknown. We tested experimentally whether administration of a wide-spectrum antibiotic (cephalosporine) during early development of magellanic penguin (Spheniscus magellanicus) chicks had any effect on their growth rates in the wild. Chicks that were injected in two occasions with cephalosporine grew faster than control untreated chicks. The positive effect of medication on nestling growth disappeared after the treatment ceased, did not alter haematological indices indicative of health status, had no influence on chick survival until near independence and was related to a changed bacterial composition of the faecal microbiota of treated chicks when compared with that from control chicks. These results were similar to those obtained for poultry with antimicrobials promoting growth and chick nutrient assimilation rates. Gram-positive bacilli in the diphtheroid genus Corynebacterium are likely candidates to cause decreased growth rates in magellanic penguin chicks. [source]

High-sensitivity detection of oxytetracycline using light scattering agglutination assay with aptasensor

ELECTROPHORESIS, Issue 18 2010
Keesung Kim
Abstract We present an aptamer-based biosensor (aptasensor) for rapid and high-sensitive detection of oxytetracycline (OTC) antibiotic in PBS inside a Y-channel PDMS microfluidic device. The detection was made by real-time monitoring of the agglutination assay of ssDNA aptamer-conjugated polystyrene latex microspheres with proximity optical fibers. The agglutination assay was performed with serially diluted OTC antibiotic solutions using highly carboxylated polystyrene particles of 920,nm diameter conjugated with OTC-binding ssDNA aptamer. Proximity optical fibers were used to measure the increase in 45° forward light scattering of the aggregated particles by fixing them around the viewing cell of the device with stable angle and distance to the detector. The detection limit was around 100,ppb for the current aptasensor system with the detection time less than 3,min. [source]

Abundance of six tetracycline resistance genes in wastewater lagoons at cattle feedlots with different antibiotic use strategies

ENVIRONMENTAL MICROBIOLOGY, Issue 1 2007
Nicholas Peak
Summary The abundance of six tetracycline resistance genes tet(O), tet(Q), tet(W), tet(M), tet(B) and tet(L), were quantified over time in wastewater lagoons at concentrated animal feeding operations (CAFO) to assess how feedlot operation affects resistance genes in downstream surface waters. Eight lagoons at five cattle feedlots in the Midwestern United States were monitored for 6 months. Resistance and 16S-rRNA gene abundances were quantified using real-time PCR, and physicochemical lagoon conditions, tetracycline levels, and other factors (e.g. feedlot size and weather conditions) were monitored over time. Lagoons were sorted according to antibiotic use practice at each site, and designated as ,no-use', ,mixed-use' or ,high-use' for comparison. High-use lagoons had significantly higher detected resistance gene levels (tetR; 2.8 × 106 copies ml,1) relative to no-use lagoons (5.1 × 103 copies ml,1; P < 0.01) and mixed-use lagoons (7.3 × 105 copies ml,1; P = 0.076). Bivariate correlation analysis on pooled data (n = 54) confirmed that tetR level strongly correlated with feedlot area (r = 0.67, P < 0.01) and ,total' bacterial 16S-rRNA gene level in each lagoon (r = 0.51, P < 0.01), which are both characteristic of large CAFOs. tet(M) was the most commonly detected gene, both in absolute number and normalized to 16S-rRNA gene level, although tet(O), tet(Q) and tet(W) levels were also high in the mixed and high-use lagoons. Finally, resistance gene levels were highly seasonal with abundances being 10,100 times greater in the autumn versus the summer. Results show that antibiotic use strategy strongly affects both the abundance and seasonal distribution of resistance genes in associated lagoons, which has implications on water quality and feedlot management practices. [source]

Binding of ciprofloxacin by humic substances: A molecular dynamics study

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2010
Ludmilla Aristilde
Abstract A comprehensive assessment of the potential impacts of antimicrobials released into the environment requires an understanding of their sequestration by natural particles. Of particular interest are the strong interactions of antimicrobials with natural organic matter (NOM), which are believed to reduce their bioavailability, retard their abiotic and biotic degradation, and facilitate their persistence in soils and aquatic sediments. Molecular dynamics (MD) relaxation studies of a widely used fluoroquinolone antibiotic, ciprofloxacin (Cipro), interacting with a model humic substance (HS) in a hydrated environment, were performed to elucidate the mechanisms of these interactions. Specifically, a zwitterionic Cipro molecule, the predominant species at circumneutral pH, was reacted either with protonated HS or deprotonated HS bearing Ca, Mg, or Fe(II) cations. The HS underwent conformational changes through rearrangements of its hydrophobic and hydrophilic regions and disruption of its intramolecular H-bonds to facilitate favorable intermolecular H-bonding interactions with Cipro. Complexation of the metal cations with HS carboxylates appeared to impede binding of the positively charged amino group of Cipro with these negatively charged HS complexation sites. On the other hand, an outer-sphere complex between Cipro and the HS-bound cation led to ternary Cipro,metal,HS complexes in the case of Mg,HS and Fe(II),HS, but no such bridging interaction occurred with Ca,HS. The results suggested that the ionic potential (valence/ionic radius) of the divalent cation may be a determining factor in the formation of the ternary complex, with high ionic potential favoring the bridging interaction. Environ. Toxicol. Chem. 2010;29:90,98. © 2009 SETAC [source]

Molecular modeling of metal complexation by a fluoroquinolone antibiotic

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2008
Ludmilla Aristilde
Abstract An understanding of the factors controlling the chemodynamics of fluoroquinolone antibiotics in different environmental matrices is a necessary prerequisite to the assessment of their potential impact on nontarget organisms in soils and receiving waters. Of particular interest are the complexes formed between fluoroquinolones and metal cations, which are believed to be important in the mechanism of sequestration of the antibiotic by minerals and natural organic matter. The structures of these complexes have not been fully resolved by conventional spectroscopy; therefore, molecular simulations may provide useful complementary insights. We present results from apparently the first molecular dynamics simulations of a widely used fluoroquinolone antibiotic, ciprofloxacin (Cipro), in aqueous complexes with five metal cations typically found in soils and surface waters: Ca2+, Mg2+, Fe2+, Na+, and K+. The interatomic potential functions employed in the simulations were validated by comparison with available structural data for solid-phase Cipro-hexahydrate and for the metal cations in aqueous solution. Although no comprehensive structural data on the aqueous complexes appear to be available, properties of the metal complexes predicted by our simulations agree with available data for solid-phase metal,Cipro complexes. Our results indicate that the ionic potential of the metal cation controls the stability of the complex formed and that the hydration number of the metal cation in aqueous solution determines its coordination number with O atoms in the metal,Cipro complex. In respect to environmental chemodynamics, our results imply that Cipro will form two configurations of bidendate chelates with metal centers on exposed surfaces of mineral oxides, water-bridged surface complexes with exchangeable cations in clay mineral interlayers, and cation-bridged complexes with functional groups in natural organic matter. [source]

Dissipation kinetics and mobility of chlortetracycline, tylosin, and monensin in an agricultural soil in Northumberland County, Ontario, Canada

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2006
Jules C. Carlson
Abstract A robust high-throughput method was refined to extract three growth-promoting antibiotics, tylosin (TYL), chlortetracycline (CTC), and monensin (MON), from soil. Analysis was performed by electrospray liquid chromatography tandem mass spectrometry. Soil dissipation rate studies were performed in a farm field soil for antibiotics applied with and without manure. Tylosin, CTC, and MON followed first-order dissipation kinetics with half-lives of 4.5, 24, and 3.3 d, respectively, with the addition of manure and 6.1, 21, and 3.8 d, respectively, without manure. Manure application significantly increased TYL dissipation rate, perhaps because of the introduced microbial flora, but had no significant effect on CTC or MON. Monensin dissipation half-life was found to be much shorter in the field study than in a controlled laboratory study, perhaps because of differences in microbial communities. The antimicrobials were not highly mobile. Chlortetracycline was the only antibiotic detected at 25 to 35 cm depth and only up to 2% of the initial concentration in a sandy loam soil. These antibiotics are therefore expected to degrade primarily in agricultural soils before moving to greater depths or to groundwater in significant concentrations in most agricultural systems. [source]

Synthesis of Nonwoven Nanofibers by Electrospinning , A Promising Biomaterial for Tissue Engineering and Drug Delivery,

ADVANCED ENGINEERING MATERIALS, Issue 8 2010
N. Naveen
PHB nanofibers are synthesized by electrospinning of a PHB solution prepared using HFIP as the solvent. The nanofibrous scaffold supports rapid cell growth with normal morphology and attains a viability of 87% after 48,h. Kanamycin sulphate-loaded PHB nanofiber mats are synthesized, with the antibiotic on the surface and sandwiched within the nanofiber mats: their antimicrobial property is proved by the good zone of inhibition tested against Staphylococcus aureus. The drug shows more than 95% release within 8,h. These results indicate that nanofibers loaded with the antibiotic have potential applications as a template for tissue engineering and as a drug carrier. [source]

Effect of ozone on oral cells compared with established antimicrobials

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2006
Karin C. Huth
Ozone has been proposed as an alternative antiseptic agent in dentistry based on reports of its antimicrobial effects in both gaseous and aqueous forms. This study investigated whether gaseous ozone (4 × 106 µg m,3) and aqueous ozone (1.25,20 µg ml,1) exert any cytotoxic effects on human oral epithelial (BHY) cells and gingival fibroblast (HGF-1) cells compared with established antiseptics [chlorhexidine digluconate (CHX) 2%, 0.2%; sodium hypochlorite (NaOCl) 5.25%, 2.25%; hydrogen peroxide (H2O2) 3%], over a time of 1 min, and compared with the antibiotic, metronidazole, over 24 h. Cell counts, metabolic activity, Sp-1 binding, actin levels, and apoptosis were evaluated. Ozone gas was found to have toxic effects on both cell types. Essentially no cytotoxic signs were observed for aqueous ozone. CHX (2%, 0.2%) was highly toxic to BHY cells, and slightly (2%) and non-toxic (0.2%) to HGF-1 cells. NaOCl and H2O2 resulted in markedly reduced cell viability (BHY, HGF-1), whereas metronidazole displayed mild toxicity only to BHY cells. Taken together, aqueous ozone revealed the highest level of biocompatibility of the tested antiseptics. [source]

The effect of gentamicin sulphate on the fracture properties of a manually mixed bone cement

FATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 6 2007
M. BALEANI
ABSTRACT This work investigates the effect of adding gentamicin, an antibiotic, on the fracture properties of bone cement. Endurance limit, fatigue crack propagation and fracture toughness were determined for a polymethylmethacrylate-based cement, containing 10% w/w of barium sulphate as radiopacifying agent, and the same formulation modified by the addition of 4.22% w/w of gentamicin sulphate. The antibiotic does not affect the endurance limit nor the fracture toughness of the material. There are significant differences in the parameters of the Paris' law fitting the crack growth data: once the main crack is nucleated, it initially propagates at a lower rate but thereafter accelerates faster in gentamicin loaded bone cement. Despite this difference, the growth rate for the same stress intensity factor remains of the same order of magnitude in both formulations. The addition of 4.22% w/w of gentamicin sulphate to radiopaque bone cement has a negligible total effect on the fracture properties of the material. [source]

Differences in the skin peptides of the male and female Australian tree frog Litoria splendida

FEBS JOURNAL, Issue 1 2000
The discovery of the aquatic male sex pheromone splendipherin, a new antibiotic peptide caerin 1.10, together with Phe8 caerulein
The skin secretions of female and male Litoria splendida have been monitored monthly over a three-year period using HPLC and electrospray mass spectrometry. Two minor peptides are present only in the skin secretion of the male. The first of these is the female-attracting aquatic male sex pheromone that we have named splendipherin, a 25 amino acid peptide (GLVSSIGKALGGLLADVVKSKGQPA-OH). This pheromone constitutes about 1% of the total skin peptides during the breeding season (January to March), dropping to about 0.1% during the period June to November. Splendipherin attracts the female in water at a concentration of 10,11,10,9 m, and is species specific. The second peptide is a wide-spectrum antibiotic of the caerin 1 group, a 25 residue peptide (GLLSVLGSVAKHVLPHVVPVIAEKL-NH2) named caerin 1.10. The neuropeptides of L. splendida are also seasonally variable, the change identical for both the female and male. During the period October to March, the sole neuropeptide present in skin secretions is caerulein [pEQDY(SO3)TGWMDF-NH2]; this is active on smooth muscle and is also an analgaesic. During the southern winter (June to September), more than half of the caerulein is hydrolysed to [pEQDYTGWMDF-NH2], a peptide that shows no smooth muscle activity. In place of caerulein, a new peptide, Phe8 caerulein [pEQDY(SO3)TGWFDF-NH2], becomes a major component of the skin secretion. Perhaps this seasonal change is involved in thermoregulation, that is, with the initiation and maintenance of the inactive (hibernation) phase of the animal. [source]

Minimizing the release of proinflammatory and toxic bacterial products within the host: A promising approach to improve outcome in life-threatening infections

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2005
Roland Nau
Abstract Various bacterial components (e.g., endotoxin, teichoic and lipoteichoic acids, peptidoglycans, DNA) induce or enhance inflammation by stimulating the innate immune system and/or are directly toxic in eukariotic cells (e.g., hemolysins). When antibiotics which inhibit bacterial protein synthesis kill bacteria, smaller quantities of proinflammatory or toxic compounds are released in vitro and in vivo than during killing of bacteria by ,-lactams and other cell-wall active drugs. In general, high antibiotic concentrations liberate lower quantities of bacterial proinflammatory or toxic compounds than concentrations close to the minimum inhibitory concentration. In animal models of Escherichia coli Pseudomonas aeruginosa and Staphylococcus aureus peritonitis/sepsis and of Streptococcus pneumoniae meningitis, a lower release of proinflammatory bacterial compounds was associated with a reduced mortality or neuronal injury. Pre-treatment with a bacterial protein synthesis inhibitor reduced the strong release of bacterial products usually observed during treatment with a ,-lactam antibiotic. Data available strongly encourage clinical trials comparing antibiotic regimens with different release of proinflammatory/toxic bacterial products. The benefit of the approach to reduce the liberation of bacterial products should be greatest in patients with a high bacterial load. [source]