bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Comparison of Serum Teicoplanin Concentrations following Daily or Alternate Daily Dosing in Healthy Adults
Authors: Rouveix Bernard , Jehl François , Drugeon Henri , Brumpt Ivan , Caulin Evelyne 
Published: June 2004

ABSTRACT

Trough serum teicoplanin concentrations were compared in healthy adults following intravenous administration of one of two regimens: (i) 12 mg/kg of body weight every 12 h for 3 doses and then 15 mg/kg every 48 h for 4 doses (
n
= 16 subjects) or (ii) 6 mg/kg every 12 h for 2 doses and then 6 mg/kg every 24 h for 9 doses (
n
= 8 subjects). The mean ± standard deviation trough concentrations in serum on day 11 (24 and 48 h after administration of the last dose for the daily and alternate-day dosing schedules, respectively) were 16.0 ± 2.1 and 17.9 ± 3.5 mg/liter for subjects receiving the two regimens, respectively, by a fluorescence polarization immunoassay. The limits of the 95% confidence interval of the difference (−0.2, 3.6 mg/liter) determined by a nonparametric test were situated above the −1.3-mg/liter maximum set difference and indicated a noninferiority of the alternate-day dosing to the daily dosing. Throughout the study the individual trough concentrations in serum in the alternate-day dosing group constantly exceeded 10 mg/liter, the presently recommended target concentration for the treatment of severe infections. The trough concentrations in the sera of all subjects were bactericidal for six
Staphylococcus aureus
strains for which teicoplanin MICs are between 0.5 and 4 mg/liter. The bactericidal activity of serum was related to total teicoplanin (protein bound and unbound). In conclusion, an alternate-day dosing schedule (15 mg/kg on alternate days following administration of a 12-mg/kg loading dose three times every 12 h) could be considered for further efficacy and safety studies.
Impact of Fluconazole Prophylaxis on Cortisol Levels in Critically Ill Surgical Patients
Authors: Magill Shelley S. , Puthanakit Thanyawee , Swoboda Sandra M. , Carson Kathryn A. , Salvatori Roberto , Lipsett Pamela A. , Hendrix Craig W. 
Published: June 2004

ABSTRACTFluconazole is widely used in the intensive care unit for prevention and treatment of fungal infections. Case reports have described an association between fluconazole and adrenal dysfunction, an important cause of morbidity and mortality in critically ill patients. We sought to determine whether 400 mg of fluconazole per day administered to critically ill surgical patients was associated with a reduction in cortisol levels. Cortisol levels were measured in stored plasma specimens drawn from 154 critically ill surgical patients randomized in 1998-1999 to receive fluconazole or placebo for the prevention of candidiasis. The primary outcome measure was the median plasma cortisol level ≥1 day after study drug initiation (MPCL). Secondary outcomes were adrenal dysfunction, defined as an MPCL of <15 μg/dl, changes in cortisol levels over time, and mortality. The median MPCL was 15.75 μg/dl (interquartile range [IQR], 11.65 to 21.33 μg/dl) in 79 patients randomized to fluconazole and 16.71 μg/dl (IQR, 11.67 to 23.00 μg/dl) in 75 patients randomized to placebo (P= 0.52). Patients randomized to fluconazole did not have significantly increased odds of adrenal dysfunction compared to patients randomized to placebo (odds ratio, 0.98; 95% confidence interval, 0.48 to 2.01). Randomization to fluconazole was not associated with a significant difference in cortisol level changes over time. Mortality was not different between patients with and without adrenal dysfunction, nor was it different between patients with adrenal dysfunction who were randomized to fluconazole and those randomized to placebo. Fluconazole prophylaxis in this population of critically ill surgical patients did not result in significant adrenal dysfunction.
Candida glabrata erg1
Mutant with Increased Sensitivity to Azoles and to Low Oxygen Tension
Authors: Tsai Huei-Fung , Bard Martin , Izumikawa Koichi , Krol Anna A. , Sturm Aaron M. , Culbertson Nicholas T. , Pierson Charles A. , Bennett John E. 
Published: June 2004

ABSTRACT

A
Candida glabrata erg1
(
Cgerg1
) mutant, CgTn201S, was identified by transposon mutagenesis and by increased fluconazole susceptibility.
CgERG1
encodes a 489-amino-acid protein which, on the basis of its homology with
Saccharomyces cerevisiae ERG1
, is a squalene epoxidase essential for ergosterol synthesis. Interruption following codon 475 of CgErg1p decreased the ergosterol content by 50%; caused accumulation of the squalene precursor; increased the levels of susceptibility to fluconazole, itraconazole, and terbinafine; increased the level of resistance to amphotericin B; increased the levels of rhodamine 6G and [
3
H]-fluconazole uptake; reduced the level of growth; and blocked growth under conditions of low oxygen tension. In addition, CgTn201S efficiently took up exogenous cholesterol from cholesterol-containing serum. Cholesterol constituted 34% of the extractable sterols in CgTn201S when it was grown aerobically on serum-containing medium. Under the same conditions,
C. albicans
contained only 0.1 to 1.2% cholesterol. Exogenous sterols also restored growth under conditions of low oxygen tension. Finally, complementation of the
Cgerg1
mutation restored the levels of [
3
H]fluconazole uptake and drug susceptibility to wild-type levels.
Beneficial Influence of Platelets on Antibiotic Efficacy in an In Vitro Model ofStaphylococcus aureus-Induced Endocarditis
Authors: Mercier Renee-Claude , Dietz Robert M. , Mazzola Jory L. , Bayer Arnold S. , Yeaman Michael R. 
Published: June 2004

ABSTRACTPlatelets contribute to antimicrobial host defense against infective endocarditis (IE) by releasing platelet microbicidal proteins (PMPs). We investigated the influence of thrombin-stimulated human platelets on the evolution of simulated IE in the presence and absence of vancomycin or nafcillin.Staphylococcus aureusstrains differing in intrinsic susceptibility to PMPs or antibiotics were studied: ISP479C (thrombin-induced PMP-1 [tPMP-1] susceptible; nafcillin and vancomycin susceptible), ISP479R (tPMP-1 resistant; nafcillin and vancomycin susceptible), and GISA-NJ (tPMP-1 intermediate-susceptible; vancomycin intermediate-susceptible). Platelets were introduced and thrombin activated within the in vitro IE model 30 min prior to inoculation withS. aureus. At 0 to 24 h postinoculation, bacterial densities in chamber fluid and simulated endocardial vegetations (SEVs) were quantified and compared among groups. Activated platelets alone, or in combination with antibiotics, inhibited the proliferation of ISP479C in chamber fluid or SEVs over the initial 4-h period (P< 0.05 versus controls). Moreover, nafcillin-containing regimens exerted inhibitory effects beyond 4 h against ISP479C in both model phases. By comparison, activated platelets inhibited GISA-NJ proliferation in SEVs but not in chamber fluid. The combination of platelets plus nafcillin or vancomycin significantly inhibited proliferation of the GISA-NJ strain in SEVs compared to the effect of platelets or antibiotics alone (P< 0.05). In contrast, platelets did not significantly alter the antistaphylococcal efficacies of nafcillin or vancomycin against ISP479R. These data support our hypothesis that a beneficial antimicrobial effect may result from the interaction among platelets, PMPs, and anti-infective agents against antibiotic-susceptible or -resistant staphylococci that exhibit a tPMP-1-susceptible or -intermediate-susceptible phenotype.
Panel of
Bacillus subtilis
Reporter Strains Indicative of Various Modes of Action
Authors: Hutter Bernd , Fischer Christina , Jacobi Alexander , Schaab Christoph , Loferer Hannes 
Published: June 2004

ABSTRACT

In a recent project, we collected the transcriptional profiles of
Bacillus subtilis
168 after treatment with a large set of diverse antibacterial agents. One result of the data analysis was the identification of marker genes that are indicative of certain compounds or compound classes. We cloned these promoter regions in front of a luciferase reporter gene and reintroduced the constructs individually into the
B. subtilis
chromosome. Strains were analyzed for their responsiveness after treatment with a set of 37 antibacterials. Twelve functional reporter strains were generated that were selectively and significantly upregulated by the compounds. The selectivity of the reporter strains ranged from generic pathways like protein biosynthesis, cell wall biosynthesis, and fatty acid biosynthesis to compound classes (quinolones and glycopeptides) and individual compounds (rifampin, cycloserine, and clindamycin). Five of the strains are amenable for high-throughput applications, e.g., pathway-specific screening. In summary, we successfully generated
B. subtilis
reporter strains that are indicative of the mechanisms of action of various classes of antibacterials. The set of reporter strains presented herein can be used for mode-of-action analyses and for whole-cell screening of compound libraries in a mode-of-action-specific manner.
Antibacterial Effects of Amoxicillin-Clavulanate against
Streptococcus pneumoniae
and
Haemophilus influenzae
Strains for Which MICs Are High, in an In Vitro Pharmacokinetic Model
Authors: MacGowan Alasdair P. , Noel Alan R. , Rogers Chris A. , Bowker Karen E. 
Published: June 2004

ABSTRACT

The antibacterial effect of amoxicillin-clavulanate in two formulations, pharmacokinetically enhanced 16:1 amoxicillin-clavulanate twice a day (b.i.d.) and standard 7:1 amoxicillin-clavulanate b.i.d., were studied in an in vitro pharmacokinetic model of infection. Five strains of
Streptococcus pneumoniae
and two of
Haemophilus influenzae
, all associated with raised MICs (2 to 8 mg/liter), were used. The antibacterial effect was measured over 24 h by the area under the bacterial kill curve (AUBKC) and the log change in viable count at 24 h (Δ24). A high 10
8
CFU/ml and low 10
6
CFU/ml initial inocula were used. Employing the Δ24 effect measure, the time above MIC (T>MIC) 50% maximum effect (EC
50
) for
S. pneumoniae
was in the range 21 to 28% with an 80% maximal response of 41 to 51%, for the AUBKC measure, the value was 26 to 39%, irrespective of inoculum. For
H. influenzae
, the T>MIC EC
50
was 28 to 37%, and the 80% maximum response was 32 to 48% for the Δ24 measure and 20 to 48% for AUBKC. The maximum response occurred at a T>MIC of 50 to 60% for both species and inocula. The
S. pneumoniae
data were analyzed by analysis of variance to assess the effect of inoculum, formulation, and MIC on antibacterial effect. Standard and enhanced formulations had different effects depending on MIC, with the standard formulation less effective at higher amoxicillin-clavulanate MICs. This is explained by the greater T>MICs of the enhanced formulation. Although resistant to amoxicillin-clavulanate by conventional breakpoints,
S. pneumoniae
and
H. influenzae
strains for which MICs are 2 or 4 mg/liter may well respond to therapy with pharmacokinetically enhanced formulation amoxicillin-clavulanate.
The Antimalarial Potential of 4-Quinolinecarbinolamines May Be Limited due to Neurotoxicity and Cross-Resistance in Mefloquine-ResistantPlasmodium falciparumStrains
Authors: Dow Geoffrey S. , Koenig Michael L. , Wolf Lesley , Gerena Lucia , Lopez-Sanchez Miriam , Hudson Thomas H. , Bhattacharjee Apurba K. 
Published: June 2004

ABSTRACTThe clinical potential of mefloquine has been compromised by reports of adverse neurological effects. A series of 4-quinolinecarbinolamines were compared in terms of neurotoxicity and antimalarial activity in an attempt to identify replacement drugs. Neurotoxicity (MTT [thiazolyl blue reduction] assay) was assessed by exposure of cultured embryonic rat neurons to graded concentrations of the drugs for 20 min. The 50% inhibitory concentration (IC50) of mefloquine was 25 μM, while those of the analogs were 19 to 200 μM. The relative (to mefloquine) therapeutic indices of the analogs were determined after using the tritiated hypoxanthine assay for assessment of the antimalarial activity of the analogs against mefloquine-sensitive (W2) and -resistant (D6 and TM91C235)Plasmodium falciparumstrains. Five analogs, WR157801, WR073892, WR007930, WR007333, and WR226253, were less neurotoxic than mefloquine and exhibited higher relative therapeutic indices (RTIs) against TM91C235 (2.9 to 12.2). Conventional quinoline antimalarials were generally less neurotoxic (IC50s of 400, 600, and 900 for amodiaquine, chloroquine, and quinine) or had higher RTIs (e.g., 30 for halofantrine against TM91C235). The neurotoxicity data for the 4-quinolinecarbinolamines were used to develop a three-dimensional (3D), function-based pharmacophore. The crucial molecular features correlated with neurotoxicity were a hydrogen bond acceptor (lipid) function, an aliphatic hydrophobic function, and a ring aromatic function specifically distributed in the 3D surface of the molecule. Mapping of the 3D structures of a series of structurally diverse quinolines to the pharmacophore allowed accurate qualitative predictions of neurotoxicity (or not) to be made. Extension of this in silico screening approach may aid in the identification of less-neurotoxic quinoline analogs.
Effect of a Combination of Clevudine and Emtricitabine with Adenovirus-Mediated Delivery of Gamma Interferon in the Woodchuck Model of Hepatitis B Virus Infection
Authors: Jacquard A. C. , Nassal M. , Pichoud C. , Ren S. , Schultz U. , Guerret S. , Chevallier M. , Werle B. , Peyrol S. , Jamard C. , Rimsky L. T. , Trepo C. , Zoulim F. 
Published: June 2004

ABSTRACT

Our aim was to evaluate the antiviral effect of a combination of two nucleoside reverse transcriptase inhibitors, emtricitabine (FTC) and clevudine (L-FMAU), with the addition of an adenovirus-driven delivery of recombinant gamma interferon (IFN-γ) in the woodchuck model of hepatitis B virus infection. Six woodchuck hepatitis virus (WHV)-infected woodchucks received L-FMAU (10 mg/kg) plus FTC (30 mg/kg) intraperitoneally for 8 weeks; six other animals received in addition an intravenous injection of a recombinant adenovirus vector expressing woodchuck IFN-γ (Ad-IFN) at weeks 4 and 8. In the control group, two animals received Ad-IFN alone, two received adenovirus vector expressing the green fluorescent protein reporter gene, and one remained untreated. In less than 2 weeks, all woodchucks that received L-FMAU plus FTC showed a rapid and marked inhibition of viral replication, with a 4-log
10
drop in serum WHV DNA. In two animals, viremia remained suppressed for several months after the end of treatment. Similarly, a dramatic decrease in intrahepatic replicative intermediates of viral DNA was observed in the L-FMAU/FTC-treated groups. The additional administration of Ad-IFN led to increased inflammation in the liver but did not enhance the antiviral effect of the L-FMAU/FTC combination. In conclusion, therapies combining L-FMAU and FTC in WHV-infected woodchucks resulted in a potent and sustained antihepadnaviral effect both in the liver and in the blood circulation. However, no extra benefit of adding IFN-γ gene transduction to the L-FMAU/FTC combination could be detected.
Incidence of the Recently Described Sulfonamide Resistance Gene
sul3
among German
Salmonella enterica
Strains Isolated from Livestock and Food
Authors: Guerra Beatriz , Junker Ernst , Helmuth Reiner 
Published: June 2004

ABSTRACT

The
sul3
gene recently described in
Escherichia coli
was found in 22 of 512 (4.3%) German
Salmonella
isolates from different regions and sources and of different serotypes, antimicrobial resistance phenotypes, and genomic groups. This is the first report on the prevalence of
sul3
among
Salmonella
strains, and the findings support the strong potential of this determinant to spread within bacterial populations.
Antimicrobial Susceptibility Patterns and Macrolide Resistance Genes of β-Hemolytic Streptococci in Korea
Authors: Uh Young , Jang In Ho , Hwang Gyu Yel , Lee Mi Kyung , Yoon Kap Jun , Kim Hyo Youl 
Published: June 2004

ABSTRACT

In 540 beta-hemolytic streptococci, the rates of resistance to tetracycline, chloramphenicol, erythromycin, and clindamycin were 80.0, 22.8, 20.2, and 19.1%, respectively. Of the erythromycin-resistant isolates, 63.3% had the constitutive macrolide-lincosamide-streptogramin B (MLS
B
) resistance phenotype, 23.9% had the M phenotype, and 12.8% had the inducible MLS
B
resistance phenotype. The constitutive MLS
B
resistance phenotype with the
erm
(B) gene was dominant in Korea.
Micafungin Enhances Neutrophil Fungicidal Functions against
Candida
Pseudohyphae
Authors: Gil-Lamaignere Cristina , Salvenmoser Stefanie , Hess Regina , Müller Frank-Michael C. 
Published: June 2004

ABSTRACT

We evaluated the effect of the combination of micafungin and polymorphonuclear leukocytes (PMN) against hyphae of
Candida albicans
and
Candida dubliniensis
. Micafungin enhanced the PMN oxidative burst dose dependently. The combination was synergistic (
C. albicans
) or additive (
C. dubliniensis
); when PMN were pretreated with granulocyte-macrophage colony-stimulating factor, the combination was more effective.
Proteomic Analysis of Azole Resistance in
Candida albicans
Clinical Isolates
Authors: Hooshdaran Massoumeh Z. , Barker Katherine S. , Hilliard George M. , Kusch Harald , Morschhäuser Joachim , Rogers P. David 
Published: June 2004

ABSTRACT

Changes in protein expression within a matched set of
Candida albicans
isolates representing the acquisition of azole resistance were examined by two-dimensional polyacrylamide gel electrophoresis and peptide mass fingerprinting. Proteins differentially expressed in association with azole resistance included Grp2p, Ifd1p, Ifd4p, Ifd5p, and Erg10p, a protein involved in the ergosterol biosynthesis pathway.
pncA
Mutations in Pyrazinamide-Resistant
Mycobacterium tuberculosis
Isolates in Portugal
Authors: Portugal Isabel , Barreiro Luís , Moniz-Pereira José , Brum Laura 
Published: June 2004

ABSTRACT

The nucleotide sequences of the
pncA
genes within 55 multidrug-resistant pyrazinamide-resistant
Mycobacterium tuberculosis
clinical isolates were determined. Fifty-three out of the 55 isolates were pyrazinamidase (PZase) negative. Four strains contained a wild-type
pncA
gene, and PZase activity was undetectable in two of these strains. Seven of the 18 identified
pncA
mutations found have not been described in previous studies.
Substitutions at Methionine 220 in the 14α-Sterol Demethylase (Cyp51A) of
Aspergillus fumigatus
Are Responsible for Resistance In Vitro to Azole Antifungal Drugs
Authors: Mellado E. , Garcia-Effron G. , Alcazar-Fuoli L. , Cuenca-Estrella M. , Rodriguez-Tudela J. L. 
Published: June 2004

ABSTRACT

Five clinical isolates of
Aspergillus fumigatus
that exhibited similar patterns of reduced susceptibility to itraconazole and other triazole drugs were analyzed. Sequence analysis of genes (
cyp51A
and
cyp51B
) encoding the 14α-sterol demethylases revealed that all five strains harbored mutations in
cyp51A
resulting in the replacement of methionine at residue 220 by valine, lysine, or threonine. When the mutated
cyp51A
genes were introduced into an
A. fumigatus
wild-type strain, the transformants exhibited reduced susceptibility to all triazole agents, confirming that the mutations were responsible for the resistance phenotype.
In Vitro and Bactericidal Activities of ABT-492, a Novel Fluoroquinolone, against Gram-Positive and Gram-Negative Organisms
Authors: Almer Laurel S. , Hoffrage Jennifer B. , Keller Erika L. , Flamm Robert K. , Shortridge Virginia D. 
Published: June 2004

ABSTRACTIn vitro activities of ABT-492, ciprofloxacin, levofloxacin, trovafloxacin, moxifloxacin, gatifloxacin, and gemifloxacin were compared. ABT-492 was more potent against quinolone-susceptible and -resistant gram-positive organisms, had activity similar to that of ciprofloxacin against certain members of the familyEnterobacteriaceae, and had comparable activity against quinolone-susceptible, nonfermentative, gram-negative organisms. Bactericidal activity of ABT-492 was also evaluated.
SUBLATTICES OF LATTICES OF ORDER-CONVEX SETS, III: THE CASE OF TOTALLY ORDERED SETS
Authors: SEMENOVA MARINA , WEHRUNG FRIEDRICH 
Published: June 2004

For a partially ordered set P, let Co(P) denote the lattice of all order-convex subsets of P. For a positive integer n, we denote by [Formula: see text] (resp., SUB(n)) the class of all lattices that can be embedded into a lattice of the form [Formula: see text] where <Ti|i∈I> is a family of chains (resp., chains with at most n elements). We prove the following results:(1) Both classes [Formula: see text] and SUB(n), for any positive integer n, are locally finite, finitely based varieties of lattices, and we find finite equational bases of these varieties.(2) The variety [Formula: see text] is the quasivariety join of all the varieties SUB(n), for 1≤n<ω, and it has only countably many subvarieties. We classify these varieties, together with all the finite subdirectly irreducible members of [Formula: see text].(3) Every finite subdirectly irreducible member of [Formula: see text] is projective within [Formula: see text], and every subquasivariety of [Formula: see text] is a variety.
The Effect of Temperature on the Dynamic Impact Characteristics of Energy Absorbing Materials
Authors: Lovell David J. , Kerman Michael L. , Allen Richard C. , Liddle John W. 
Published: June 2004

A variety of different materials have been considered and implemented for occupant protection in automotive head impact countermeasures since the beginning of the five-year phase of FMVSS 201 (Upper) on September 1, 1998. Polyurethane foam has been the material of choice because of its good performance, ability to maintain properties across a wide range of temperature conditions, reasonable cost, and ability to be molded into complex shapes. In recent years, pressure to reduce costs has resulted in an increased use of lower-cost thermoplastic materials. The thermoplastic nature of some of these materials can lead to significant changes in energy management characteristics with changes in environmental conditions. This paper shows that polyurethane foams are superior at retaining their energy-absorbing characteristics over the service temperature range of 30 to 85 °C.
A Content Analysis of Librarianship Research
Authors: Koufogiannakis Denise , Slater Linda , Crumley Ellen 
Published: June 2004

Objective: To conduct a content analysis of library and information studies (LIS) literature published in 2001 and test the domains developed by Crumley and Koufogiannakis. Methods: A comprehensive list of refereed library and information studies journals was compiled and reviewed independently by two researchers to derive a list of included journals. Articles published in 2001 from included journals were independently assessed for relevancy by two researchers. Researchers separately extracted and checked data from included articles. Results: 217 LIS journals were reviewed and 107 were included; 91 journals provided data. 2664 journal articles were examined, with 807 (30.3%) classified as research. The Top 10 journals for research published in 2001 were: 1) JASIST, 2) Scientometrics, 3) Info Proc & Man; 4) Coll & Res Lib, 5) Tie: J Lib Adm/Bull Med Lib Assn, 7) Libs & Culture, 8) J Doc, 9) Tie: J Info Sci/J Acad Libr. For the period studied, descriptive research (329 out of 807 articles) was published far more frequently than any other type. The domain Information Access & Retrieval had the highest number of research articles (314/807), followed by Collections (193/807), Management (135/807), Education (95/807) and Reference (77/807). Two new possible domains were identified: Library History and Professional Issues. Conclusions: Because 36 articles fell into the domain of Professional Issues, a case can be made to add this domain to Crumley and Koufogiannakis’ taxonomy. Library History was not added as a domain because historical research is not used for evidence-based decision-making. There was no evidence to support keeping the Marketing & Promotion domain. LISA provides the best coverage of the top 10 LIS research journals identified in this study.