bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Sulfobutylether-Beta-Cyclodextrin and Voriconazole in Patients with End-Stage Renal Failure during Treatment with Two Hemodialysis Systems and Hemodiafiltration
Authors: Hafner Verena , Czock David , Burhenne Jürgen , Riedel Klaus-Dieter , Bommer Jürgen , Mikus Gerd , Machleidt Christoph , Weinreich Thomas , Haefeli Walter E. 
Published: April 2010

ABSTRACT

Sulfobutylether-beta-cyclodextrin (SBECD), a large cyclic oligosaccharide that is used to solubilize voriconazole (VRC) for intravenous administration, is eliminated mainly by renal excretion. The pharmacokinetics of SBECD and voriconazole in patients undergoing extracorporeal renal replacement therapies are not well defined. We performed a three-period randomized crossover study of 15 patients with end-stage renal failure during 6-hour treatment with Genius dialysis, standard hemodialysis, or hemodiafiltration using a high-flux polysulfone membrane. At the start of renal replacement therapy, the patients received a single 2-h infusion of voriconazole (4 mg per kg of body weight) solubilized with SBECD. SBECD, voriconazole, and voriconazole-
N
-oxide concentrations were quantified in plasma and dialysate samples by high-performance liquid chromatography (HPLC) and by HPLC coupled to tandem mass spectrometry (LC-MS-MS) and analyzed by noncompartmental methods. Nonparametric repeated-measures analysis of variance (ANOVA) was used to analyze differences between treatment phases. SBECD and voriconazole recoveries in dialysate samples were 67% and 10% of the administered doses. SBECD concentrations declined with a half-life ranging from 2.6 ± 0.6 h (Genius dialysis) to 2.4 ± 0.9 h (hemodialysis) and 2.0 ± 0.6 h (hemodiafiltration) (
P
< 0.01 for Genius dialysis versus hemodiafiltration). Prediction of steady-state conditions indicated that even with daily hemodialysis, SBECD will still exceed SBECD exposure of patients with normal renal function by a factor of 6.2. SBECD was effectively eliminated during 6 h of renal replacement therapy by all methods, using high-flux polysulfone membranes, whereas elimination of voriconazole was quantitatively insignificant. The SBECD half-life during renal replacement therapy was nearly normalized, but the average SBECD exposure during repeated administration is expected to be still increased.
In Vitro
Activities of DC-159a, a Novel Fluoroquinolone, against
Mycobacterium
Species
Authors: Disratthakit Areeya , Doi Norio 
Published: April 2010

ABSTRACT

The
in vitro
activities of DC-159a against seven species of
Mycobacterium
were compared with moxifloxacin, gatifloxacin, levofloxacin, and rifampin. DC-159a was the most active compound against quinolone-resistant multidrug-resistant
M. tuberculosis
(MIC
90
, 0.5 μg/ml) as well as drug-susceptible isolates (MIC
90
, 0.06 μg/ml). The anti-tubercle bacilli activity of DC-159a was 4- to 32-fold more potent than those of currently available quinolones. DC-159a also demonstrated the highest activities against clinically important nontuberculous mycobacteria.
Molecular Characterization of β-Lactamase Genes and Their Genetic Structures inAcinetobacterGenospecies 3 Isolates in Taiwan
Authors: Huang Li-Yueh , Lu Po-Liang , Chen Te-Li , Chang Fang-Yee , Fung Chang-Phone , Siu L. K. 
Published: April 2010

ABSTRACTThe genetic structure of β-lactamases inAcinetobactergenospecies 3 (AG3) isolates in Taiwan was studied to analyze their high rates of resistance to β-lactams, including carbapenems (57.9%).blaIMP-1andblaIMP-8were located in a class 1 integron.blaOXA-58was bracketed by ISAba3. A novel TnpF-like integrase gene was identified upstream ofblaVEB-3. Adjacent to the 5′ sequence of theblaADCgene,folEwas identified. Four newAcinetobacter-derived cephalosporinase (ADC) enzymes were found, which clustered phylogenetically with published AG3 ADC proteins.
Low Prevalence of
fks1
Hot Spot 1 Mutations in a Worldwide Collection of
Candida
Strains
Authors: Castanheira Mariana , Woosley Leah N. , Diekema Daniel J. , Messer Shawn A. , Jones Ronald N. , Pfaller Michael A. 
Published: April 2010

ABSTRACT

We evaluated the prevalence of
fks1
hot spot (HS) 1 mutations among 133
Candida
strains from six species displaying various caspofungin MIC values (from ≤0.008 to >8 μg/ml). Only 4 (2.9%) strains displayed FKS1 HS1 amino acid substitutions: 1
C. albicans
(F641Y) among 32 isolates tested (3.1%), 1
C. glabrata
(S645P) among 34 isolates tested (2.9%), and 2
C. tropicalis
(F641S) among 12 isolates tested (16.7%). The 4 isolates displaying FKS1 HS1 alterations showed elevated caspofungin MIC results (1 to >8 μg/ml) but lower anidulafungin and micafungin MIC values (0.12 to 4 μg/ml and 0.25 to 4 μg/ml, respectively) in some instances within the wild-type MIC population, as determined using the epidemiologic cutoff values (ECV).
Candida krusei
,
C. parapsilosis
, and
C. guilliermondii
isolates tested showed no FKS1 HS1 alterations regardless of echinocandin MIC result. We additionally analyzed 8
C. albicans
and 7
C. glabrata
strains for mutations on other HS regions of
fks1
and
fks2
. Three
C. glabrata
strains showed alterations on FKS2 HS1 (two S645P and one L644W). In general, strains displaying S645P alteration showed higher echinocandin MIC values than strains harboring other mutations. Overall,
Candida
spp. strains showing caspofungin MIC values within the ECV did not display
fks
HS mutations. In contrast, strains showing alterations in this region displayed anidulafungin and/or micafungin MIC values within the wild-type population, suggesting that caspofungin could be the most sensitive agent for detection of these resistance mutations. Furthermore, results from this large, geographically diverse
Candida
spp. collection demonstrated that
fks1
HS1 mutations remain uncommon among isolates with various echinocandin MIC levels.
Discovery of a Gene Conferring Multiple-Aminoglycoside Resistance in
Escherichia coli
Authors: Davis Margaret A. , Baker Katherine N. K. , Orfe Lisa H. , Shah Devendra H. , Besser Thomas E. , Call Douglas R. 
Published: April 2010

ABSTRACT

Bovine-origin
Escherichia coli
isolates were tested for resistance phenotypes using a disk diffusion assay and for resistance genotypes using a DNA microarray. An isolate with gentamicin and amikacin resistance but with no corresponding genes detected yielded a 1,056-bp DNA sequence with the closest homologues for its inferred protein sequence among a family of 16S rRNA methyltransferase enzymes. These enzymes confer high-level aminoglycoside resistance and have only recently been described in Gram-negative bacteria.
Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate (CS-8958) versus Oseltamivir as Treatment for Children with Influenza Virus Infection
Authors: Sugaya Norio , Ohashi Yasuo 
Published: April 2010

ABSTRACT
We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.
In Vitro
Double and Triple Bactericidal Activities of Doripenem, Polymyxin B, and Rifampin against Multidrug-Resistant
Acinetobacter baumannii
,
Pseudomonas aeruginosa
,
Klebsiella pneumoniae
, and
Escherichia coli
Authors: Urban Carl , Mariano Noriel , Rahal James J. 
Published: April 2010

ABSTRACT

In vitro
double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant
Klebsiella pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
, and
Escherichia coli
isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.
Antimicrobial Susceptibilities of a Worldwide Collection of
Stenotrophomonas maltophilia
Isolates Tested against Tigecycline and Agents Commonly Used for
S. maltophilia
Infections
Authors: Farrell David J. , Sader Helio S. , Jones Ronald N. 
Published: April 2010

ABSTRACT

Antimicrobial susceptibilities were determined for 1,586 isolates of
Stenotrophomonas maltophilia
from globally diverse medical centers using the Clinical Laboratory Standards Institute broth microdilution method. The combination trimethoprim-sulfamethoxazole (96.0% of isolates susceptible at ≤2 μg/ml trimethoprim and 38 μg/ml sulfamethoxazole) and tigecycline (95.5% of isolates sussceptible at ≤2 μg/ml) were the only antimicrobials tested with >94% susceptibility in all regions. Susceptibility rates for other commonly used were lower than expected and varied geographically. This
in vitro
data supports tigecycline as a potential candidate for clinical investigations into
S. maltophilia
infections.
Altered Growth, Pigmentation, and Antimicrobial Susceptibility Properties of
Staphylococcus
aureus
Due to Loss of the Major Cold Shock Gene
cspB
Authors: Duval Brea D. , Mathew Anselmo , Satola Sarah W. , Shafer William M. 
Published: April 2010

ABSTRACT

An insertional mutation made in the major cold shock gene
cspB
in
Staphylococcus
aureus
strain COL, a methicillin-resistant clinical isolate, yielded a mutant that displayed a reduced capacity to respond to cold shock and many phenotypic characteristics of
S
.
aureus
small-colony variants: a growth defect at 37°C, a reduction in pigmentation, and altered levels of susceptibility to many antimicrobials. In particular, a
cspB
null mutant displayed increased resistance to aminoglycosides, trimethoprim-sulfamethoxazole, and paraquat and increased susceptibility to daptomycin, teicoplanin, and methicillin. With the exception of the increased susceptibility to methicillin, which was due to a complete loss of the type I staphylococcal cassette chromosome
mec
element, these properties were restored to wild-type levels by complementation when
cspB
was expressed in
trans
. Taken together, our results link a stress response protein (CspB) of
S
.
aureus
to important phenotypic properties that include resistance to certain antimicrobials.
Characterization of V36C, a Novel Amino Acid Substitution Conferring Hepatitis C Virus (HCV) Resistance to Telaprevir, a Potent Peptidomimetic Inhibitor of HCV Protease
Authors: Barbotte Laetitia , Ahmed-Belkacem Abdelhakim , Chevaliez Stéphane , Soulier Alexandre , Hézode Christophe , Wajcman Henri , Bartels Doug J. , Zhou Yi , Ardzinski Andrzej , Mani Nagraj , Rao B. Govinda , George Shelley , Kwong Ann , Pawlotsky Jean-Michel 
Published: April 2010

ABSTRACT
We characterized a novel substitution conferring moderate resistance to telaprevir, a peptidomimetic inhibitor of hepatitis C virus protease. V36C conferred a 4.0-fold increase in the telaprevir 50% inhibitory concentration in an enzyme assay and a 9.5-fold increase in the replicon model. The replication capacity of a replicon harboring V36C was close to that of the wild-type protease. This case emphasizes the complexity of hepatitis C virus resistance to protease inhibitors.
Effects of Plant Genotype and Growth Stage on the Betaproteobacterial Communities Associated with Different Potato Cultivars in Two Fields
Authors: İnceoğlu Özgül , Salles Joana Falcão , van Overbeek Leo , van Elsas Jan Dirk 
Published: April 2010

ABSTRACT

Bacterial communities in the rhizosphere are dynamic and susceptible to changes in plant conditions. Among the bacteria, the betaproteobacteria play key roles in nutrient cycling and plant growth promotion, and hence the dynamics of their community structures in the rhizosphere should be investigated. Here, the effects of plant cultivar, growth stage, and soil type on the communities associated with potato cultivars Aveka, Aventra, Karnico, Modena, Premiere, and Désirée were assessed for two different fields containing sandy soil with either a high or low organic compound content. Thus, bacterial and betaproteobacterial PCR-denaturing gradient gel electrophoresis analyses were performed to analyze the effects of plant cultivar and growth on the rhizosphere community structure. The analyses showed that in both fields all cultivars had a rhizosphere effect on the total bacterial and betaproteobacterial communities. In addition, the plant growth stage strongly affected the betaproteobacterial communities in both fields. Moreover, the community structures were affected by cultivar, and cultivars differed in physiology, as reflected in their growth rates, root development, and estimated tuber starch contents. Analyses of betaproteobacterial clone libraries constructed for two selected cultivars (one cultivar that produced low-starch-content tubers and one cultivar that produced high-starch-content tubers), as well as bulk soil, revealed that the rhizospheres of the two cultivars selected for specific bacteria, including plant-growth-promoting bacteria, such as
Variovorax
and
Achromobacter
spp. In addition, quantitative PCR-based quantification of the
Variovorax paradoxus
-specific functional gene
asfA
(involved in desulfonation) indicated that there were clear potato rhizosphere effects on the abundance of this gene. Interestingly, both cultivar type and plant growth stage affected the community under some circumstances.
Double-Blind Characterization of Non-Genome-Sequenced Bacteria by Mass Spectrometry-Based Proteomics
Authors: Jabbour Rabih E. , Deshpande Samir V. , Wade Mary Margaret , Stanford Michael F. , Wick Charles H. , Zulich Alan W. , Skowronski Evan W. , Snyder A. Peter 
Published: April 2010

ABSTRACT
Due to the possibility of a biothreat attack on civilian or military installations, a need exists for technologies that can detect and accurately identify pathogens in a near-real-time approach. One technology potentially capable of meeting these needs is a high-throughput mass spectrometry (MS)-based proteomic approach. This approach utilizes the knowledge of amino acid sequences of peptides derived from the proteolysis of proteins as a basis for reliable bacterial identification. To evaluate this approach, the tryptic digest peptides generated from double-blind biological samples containing either a single bacterium or a mixture of bacteria were analyzed using liquid chromatography-tandem mass spectrometry. Bioinformatic tools that provide bacterial classification were used to evaluate the proteomic approach. Results showed that bacteria in all of the double-blind samples were accurately identified with no false-positive assignment. The MS proteomic approach showed strain-level discrimination for the various bacteria employed. The approach also characterized double-blind bacterial samples to the respective genus, species, and strain levels when the experimental organism was not in the database due to its genome not having been sequenced. One experimental sample did not have its genome sequenced, and the peptide experimental record was added to the virtual bacterial proteome database. A replicate analysis identified the sample to the peptide experimental record stored in the database. The MS proteomic approach proved capable of identifying and classifying organisms within a microbial mixture.
Involvement of the Mannose Phosphotransferase System of
Lactobacillus plantarum
WCFS1 in Peroxide Stress Tolerance
Authors: Stevens Marc J. A. , Molenaar Douwe , de Jong Anne , de Vos Willem M. , Kleerebezem Michiel 
Published: April 2010

ABSTRACT

A
Lactobacillus plantarum
strain with a deletion in the gene
rpoN
, encoding the alternative sigma factor 54 (σ
54
), displayed a 100-fold-higher sensitivity to peroxide than its parental strain. This feature could be due to σ
54
-dependent regulation of genes involved in the peroxide stress response. However, transcriptome analyses of the wild type and the mutant strain during peroxide exposure did not support such a role for σ
54
. Subsequent experiments revealed that the impaired expression of the mannose phosphotransferase system (PTS) operon in the
rpoN
mutant caused the observed increased peroxide sensitivity.
Fate of aPseudomonas savastanoipv. savastanoi Type III Secretion System Mutant in Olive Plants (Olea europaeaL.)
Authors: Pérez-Martínez Isabel , Rodríguez-Moreno Luis , Lambertsen Lotte , Matas Isabel M. , Murillo Jesús , Tegli Stefania , Jiménez Antonio J. , Ramos Cayo 
Published: April 2010

ABSTRACTPseudomonas savastanoipv. savastanoi strain NCPPB 3335 is a model bacterial pathogen for studying the molecular basis of disease production in woody hosts. We report the sequencing of thehrpS-to-hrpZregion of NCPPB 3335, which has allowed us to determine the phylogenetic position of this pathogen with respect to previously sequencedPseudomonas syringae hrpclusters. In addition, we constructed a mutant of NCPPB 3335, termed T3, which carries a deletion from the 3′ end of thehrpSgene to the 5′ end of thehrpZoperon. Despite its inability to multiply in olive tissues and to induce tumor formation in woody olive plants,P.savastanoipv. savastanoi T3 can induce knot formation on young micropropagated olive plants. However, the necrosis and formation of internal open cavities previously reported in knots induced by the wild-type strain were not observed in those induced byP.savastanoipv. savastanoi T3. Tagging ofP.savastanoipv. savastanoi T3 with green fluorescent protein (GFP) allowed real-time monitoring of its behavior on olive plants. In olive plant tissues, the wild-type strain formed aggregates that colonized the intercellular spaces and internal cavities of the hypertrophic knots, while the mutant T3 strain showed a disorganized distribution within the parenchyma of the knot. Ultrastructural analysis of knot sections revealed the release of extensive outer membrane vesicles from the bacterial cell surface of theP.savastanoipv. savastanoi T3 mutant, while the wild-type strain exhibited very few vesicles. This phenomenon has not been described before for any other bacterial phytopathogen during host infection.
Carbohydrate Metabolism in Mutants of the Cyanobacterium
Synechococcus elongatus
PCC 7942 Defective in Glycogen Synthesis
Authors: Suzuki Eiji , Ohkawa Hajime , Moriya Katsuya , Matsubara Tatsuya , Nagaike Yukari , Iwasaki Ikuko , Fujiwara Shoko , Tsuzuki Mikio , Nakamura Yasunori 
Published: April 2010

ABSTRACT

ADP-glucose pyrophosphorylase (AGPase) and glycogen synthase (GS) catalyze the first two reactions of glycogen synthesis in cyanobacteria. Mutants defective in each of these enzymes in
Synechococcus elongatus
PCC 7942 were constructed and characterized. Activities of the corresponding enzymes in the selected mutants were virtually undetectable, and their ability to synthesize glycogen was entirely abolished. The maximal activities of photosynthetic O
2
evolution and the rates of respiration in the dark were significantly decreased in the mutants compared to those in wild-type cells. Addition of 0.2 M NaCl or 3 mM H
2
O
2
to liquid cultures markedly inhibited the growth of the AGPase and GS mutants, while the same treatment had only marginal effects on the wild type. These results suggest a significant role for storage polysaccharides in tolerance to salt or oxidative stress.
Bacterial Capture by Peptide-Mimetic Oligoacyllysine Surfaces
Authors: Rotem Shahar , Raz Nili , Kashi Yechezkel , Mor Amram 
Published: April 2010

ABSTRACT

Most procedures for detecting pathogens in liquid media require an initial concentration step. However, poor recovery efficiencies of conventional methods, such as filtration, often lead to low sensitivity. Here, we describe a strategy for concentrating bacteria using their binding affinity for an oligoacyllysine (OAK), a novel peptide-mimetic antimicrobial compound. We show that the resin-linked OAK (ROAK) efficiently captures a variety of pathogens in different media, upon brief incubation with ROAK beads or after continuous flow through a ROAK-packed column. Using
Escherichia coli
expressing green fluorescent protein, we show that binding occurs rapidly during incubation and persists after filtration as visualized by confocal microscopy. The high binding affinity of bacteria was confirmed by surface plasmon resonance technology using an OAK-linked chip. ROAK-bound bacteria remained viable and were readily identifiable by real-time PCR after ethanol elution. A single ROAK bead is estimated to capture about 3,000 bacterial cells in culture medium, in contaminated saline or tap water. ROAK beads can be regenerated for multiple uses after brief ethanol treatment. Collectively, the data support the notion that OAK-based coating of polymeric surfaces might represent a useful means for medium filtration as well as for concentration of bacteria.