bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative In Vitro Activities of Ciprofloxacin, Gemifloxacin, Grepafloxacin, Moxifloxacin, Ofloxacin, Sparfloxacin, Trovafloxacin, and Other Antimicrobial Agents against Bloodstream Isolates of Gram-Positive Cocci
Authors: Hardy Dwight , Amsterdam Daniel , Mandell Lionel A. , Rotstein Coleman 
Published: July 2002

ABSTRACT

The in vitro activity of gemifloxacin against 316 bloodstream isolates of staphylococci, pneumococci, and enterococci was compared with the activities of six fluoroquinolones and three other antimicrobial agents. Of the antimicrobial agents tested, gemifloxacin was the most potent against penicillin-intermediate and -resistant pneumococci, methicillin-susceptible and -resistant
Staphylococcus epidermidis
isolates, and coagulase-negative staphylococci.
Compartmental Pharmacokinetics and Tissue Distribution of Multilamellar Liposomal Nystatin in Rabbits
Authors: Groll Andreas H. , Mickiene Diana , Werner Kathy , Petraitiene Ruta , Petraitis Vidmantas , Calendario Myrna , Field-Ridley Aida , Crisp Jeremy , Piscitelli Stephen C. , Walsh Thomas J. 
Published: July 2002

ABSTRACT

The plasma pharmacokinetics of multilamellar liposomal nystatin were studied in normal, catheterized rabbits after single and multiple daily intravenous administration of dosages of 2, 4, and 6 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of liposomal nystatin were measured as those of nystatin by a validated high-performance liquid chromatography method, and plasma concentration data were fitted into a two-compartment open model. Across the investigated dosage range, liposomal nystatin demonstrated nonlinear kinetics with more than proportional increases in the AUC
0–24
and decreasing clearance, consistent with dose-dependent tissue distribution and/or a dose-dependent elimination process. After single-dose administration, the mean
C
max
increased from 13.07 μg/ml at 2 mg/kg to 41.91 μg/ml at 6 mg/kg (
P
< 0.001); the AUC
0–24
changed from 11.65 to 67.44 μg · h/ml (
P
< 0.001), the

V
d

changed from 0.205 to 0.184 liters/kg (not significant), the CL

t

from 0.173 to 0.101 liters/kg · h (
P
< 0.05), and terminal half-life from 0.96 to 1.51 h (
P
< 0.05). There were no significant changes in pharmacokinetic parameters after multiple dosing over 14 days. Assessment of tissue concentrations of nystatin near peak plasma levels after multiple dosing over 15 days revealed preferential distribution to the lungs, liver, and spleen at that time point. Substantial levels were also found in the urine, raising the possibility that renal excretion may play a significant role in drug elimination. Liposomal nystatin administered to rabbits was well tolerated and displayed nonlinear pharmacokinetics, potentially therapeutic peak plasma concentrations, and substantial penetration into tissues. Pharmacokinetic parameters were very similar to those observed in patients, thus validating results derived from infection models in the rabbit and allowing inferences to be made about the treatment of invasive fungal infections in humans.
Inhibition of Human Rhinovirus-Induced Cytokine Production by AG7088, a Human Rhinovirus 3C Protease Inhibitor
Authors: Zalman L. S. , Brothers M. A. , Dragovich P. S. , Zhou R. , Prins T. J. , Worland S. T. , Patick A. K. 
Published: July 2002

ABSTRACTSymptom severity in patients with human rhinovirus (HRV)-induced respiratory illness is associated with elevated levels of the inflammatory cytokines interleukin-6 (IL-6) and IL-8. AG7088 is a novel, irreversible inhibitor of the HRV 3C protease. In this study, AG7088 was tested for its antiviral activity and ability to inhibit the production of IL-6 and IL-8 in a human bronchial epithelial cell line, BEAS-2B. Infection of BEAS-2B cells with HRV 14 resulted in the production of both infectious virus and the cytokines IL-6 and IL-8. Treatment of HRV 14-infected cells with AG7088 resulted in a statistically significant (P, <0.05) dose-dependent reduction in the levels of infectious virus as well as IL-6 and IL-8 released into the cell supernatant compared to the results obtained for compound-free infected cells. AG7088 was also able to inhibit the replication of HRV 2 and 16 in BEAS-2B cells. In time-of-addition studies, AG7088 could be added as late as 14 to 26 h after HRV 14 infection of BEAS-2B cells and still result in a statistically significant (P, <0.05) reduction in the levels of infectious virus, IL-6, and IL-8 compared to the results obtained for compound-free infected cells. These findings have implications for the development of an antirhinovirus agent that may not only block virus replication but also diminish symptoms.
Glycopeptide-Resistant
Enterococcus faecium
BM4416 Is a VanD-Type Strain with an Impaired
d
-Alanine:
d
-Alanine Ligase
Authors: Perichon Bruno , Casadewall Barbara , Reynolds Peter , Courvalin Patrice 
Published: July 2002

ABSTRACT

VanD-type
Enterococcus faecium
BM4416 was constitutively resistant to vancomycin and to teicoplanin by synthesis of peptidoglycan precursors ending in
d
-alanyl–
d
-lactate. Like
E. faecium
BM4339, the only VanD-type strain described so far, BM4416 produced an impaired
d
-alanine:
d
-alanine ligase. Unlike for BM4339, which had a 5-bp insertion in
ddl
, inactivation of the gene in BM4416 was due to insertion of IS
19
.
Does Long-Term Itraconazole Prophylaxis Result in In Vitro Azole Resistance in Mucosal
Candida albicans
Isolates from Persons with Advanced Human Immunodeficiency Virus Infection?
Authors: Goldman Mitchell , Cloud Gretchen A. , Smedema Melinda , LeMonte Ann , Connolly Patricia , McKinsey David S. , Kauffman Carol A. , Moskovitz Bruce , Wheat L. Joseph ,   The National Institute of Allergy and Infectious Diseases Mycoses Study Group
Published: July 2002

ABSTRACT

The effects of prolonged itraconazole exposure on the susceptibility of
Candida albicans
isolates to itraconazole and fluconazole have not been well characterized. A recent placebo-controlled study of long-term itraconazole antifungal prophylaxis in persons with advanced human immunodeficiency virus infection afforded the opportunity to address this question. Mucosal
Candida
sp. isolates were obtained from subjects who developed oropharyngeal or esophageal candidiasis, and in vitro susceptibilities of the last isolate obtained at removal from the study as a prophylaxis failure were compared in itraconazole and placebo recipients. More subjects in the placebo group (74 of 146 [51%]) than in the itraconazole group (51 of 149 [34%]) developed mucosal candidiasis (
P
= 0.004). A total of 112 isolates were recovered from 56 of the 74 (76%) subjects with mucosal candidiasis assigned to the placebo group, compared to 97 isolates from 45 of the 51 (88%) subjects in the itraconazole group.
C. albicans
accounted for 98% of isolates in the placebo group and 89% of isolates in the itraconazole group. The itraconazole MIC at which 50% of the isolates tested were inhibited (MIC
50
) for last-episode isolates from the itraconazole group was 0.125 μg/ml compared to 0.015 μg/ml for the placebo group subjects,
P
= 0.0001. The MIC
50
of fluconazole for the last isolates from the itraconazole group was 1.5 μg/ml compared to 0.5 μg/ml for the placebo subjects (
P
= 0.005). A lower proportion of isolates recovered from subjects on itraconazole therapy were classified as susceptible to itraconazole (63%) compared to isolates from the placebo group (96%) (
P
= 0.001). Similarly, a lower proportion of
C. albicans
isolates from subjects on itraconazole therapy were susceptible to fluconazole (78%) compared to isolates from the placebo group (96%) (
P
= 0.01). Also, the proportion of isolates that were not fully susceptible to itraconazole or fluconazole was greater in patients assigned to the itraconazole group than the placebo group (itraconazole susceptibility, 37 and 4%, respectively (
P
= 0.001); fluconazole susceptibility, 23 and 4%, respectively (
P
= 0.01). In conclusion, long-term itraconazole prophylaxis in patients with AIDS is associated with reduction in susceptibility to itraconazole and cross-resistance to fluconazole.
Indinavir Population Pharmacokinetics in Plasma and Cerebrospinal Fluid
Authors: Letendre Scott L. , Capparelli Edmund V. , Ellis Ronald J. , McCutchan J. Allen ,   The HIV NEUROBEHAVIORAL RESEARCH CENTER GROUP
Published: July 2002

ABSTRACT
Plasma and cerebrospinal fluid (CSF) indinavir concentrations were measured by high-performance liquid chromatography. The median concentration in plasma exceeded that in CSF 10-fold. The modeled CSF curve was flat at 155 nM, and the estimated ratio of the areas under the CSF and plasma concentration-time curves was 6%. We conclude that CSF indinavir concentrations are lower than levels in plasma but exceed the clinical 95% inhibitory concentration range.
Antibiotic Activity and Characterization of BB-3497, a Novel Peptide Deformylase Inhibitor
Authors: Clements John M. , Beckett R. Paul , Brown Anthony , Catlin Graham , Lobell Mario , Palan Shilpa , Thomas Wayne , Whittaker Mark , Wood Stephen , Salama Sameeh , Baker Patrick J. , Rodgers H. Fiona , Barynin Vladimir , Rice David W. , Hunter Michael G. 
Published: July 2002

ABSTRACT

Peptide deformylase (PDF) is an essential bacterial metalloenzyme which deformylates the
N
-formylmethionine of newly synthesized polypeptides and as such represents a novel target for antibacterial chemotherapy. To identify novel PDF inhibitors, we screened a metalloenzyme inhibitor library and identified an
N
-formyl-hydroxylamine derivative, BB-3497, and a related natural hydroxamic acid antibiotic, actinonin, as potent and selective inhibitors of PDF. To elucidate the interactions that contribute to the binding affinity of these inhibitors, we determined the crystal structures of BB-3497 and actinonin bound to
Escherichia coli
PDF at resolutions of 2.1 and 1.75 Å, respectively. In both complexes, the active-site metal atom was pentacoordinated by the side chains of Cys 90, His 132, and His 136 and the two oxygen atoms of
N
-formyl-hydroxylamine or hydroxamate. BB-3497 had activity against gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus
and vancomycin-resistant
Enterococcus faecalis
, and activity against some gram-negative bacteria. Time-kill analysis showed that the mode of action of BB-3497 was primarily bacteriostatic. The mechanism of resistance was via mutations within the formyltransferase gene, as previously described for actinonin. While actinonin and its derivatives have not been used clinically because of their poor pharmacokinetic properties, BB-3497 was shown to be orally bioavailable. A single oral dose of BB-3497 given 1 h after intraperitoneal injection of
S. aureus
Smith or methicillin-resistant
S. aureus
protected mice from infection with median effective doses of 8 and 14 mg/kg of body weight, respectively. These data validate PDF as a novel target for the design of a new generation of antibacterial agents.
Characterization of P55, a Multidrug Efflux Pump in
Mycobacterium bovis
and
Mycobacterium tuberculosis
Authors: Silva Pedro E. A. , Bigi Fabiana , de la Paz Santangelo Marı́a , Romano Maria Isabel , Martı́n Carlos , Cataldi Angel , Aı́nsa José A. 
Published: July 2002

ABSTRACT

The
Mycobacterium bovis P55
gene, located downstream from the gene that encodes the immunogenic lipoprotein P27, has been characterized. The gene was identical to the open reading frame of the Rv1410c gene in the genome of
Mycobacterium tuberculosis
H37Rv, annotated as a probable drug efflux protein. Genes similar to
P55
were present in all species of the
M. tuberculosis
complex and other mycobacteria such as
Mycobacterium leprae
and
Mycobacterium avium
. By Western blotting, P55 was located in the membrane fraction of
M. bovis
. When transformed into
Mycobacterium smegmatis
after cloning, P55 conferred aminoglycoside and tetracycline resistance. The levels of resistance to streptomycin and tetracycline conferred by P55 were decreased in the presence of the protonophore carbonyl cyanide
m
-chlorophenylhydrazone and the pump inhibitors verapamil and reserpine.
M. smegmatis
cells expressing the plasmid-encoded P55 accumulated less tetracycline than the control cells. We conclude that P55 is a membrane protein implicated in aminoglycoside and tetracycline efflux in mycobacteria.
DNA Transformation of
Leishmania infantum
Axenic Amastigotes and Their Use in Drug Screening
Authors: Sereno Denis , Roy Gaétan , Lemesre Jean Loup , Papadopoulou Barbara , Ouellette Marc 
Published: July 2002

ABSTRACT

Protocols for DNA electroporation in
Leishmania
promastigote cells are well established. More recently, in vitro culture of axenic
Leishmania
amastigotes became possible. We have established conditions for DNA transformation of axenically grown
Leishmania infantum
amastigotes. Parameters for DNA electroporation of
Leishmania
axenic amastigotes were systematically studied using luciferase-mediated transient transfection. Cell lines expressing stable luciferase activity were then selected, and their ability to be used in an in vitro drug screening procedure was determined. A model was established, using axenic amastigotes expressing luciferase activity, for rapidly determining the activity of drugs directly against both axenic and intracellular amastigotes. For intracellular amastigotes, the 50% effective concentrations of pentamidine, sodium stibogluconate (Pentostam), meglumine (Glucantime), and potassium antimonyl tartrate determined with the luciferase assay were 0.2 μM (0.12 μg/ml), 55 μg/ml, 95 μg/ml, and 0.12 μg/ml, respectively; these values are in agreement with values determined by more labor-intensive staining methods. We also showed the usefulness of luciferase-expressing parasites for analyzing drug resistance. The availability of luciferase-expressing amastigotes for use in high-throughput screening should facilitate the search for new antileishmanial drugs.
Human Malaria in Immunocompromised Mice: New In Vivo Model for Chemotherapy Studies
Authors: Moreno A. , Badell E. , Van Rooijen N. , Druilhe P. 
Published: July 2002

ABSTRACT

We have recently designed a new
Plasmodium falciparum
mouse model and documented its potential for the study of immune effector mechanisms. In order to determine its value for drug studies, we evaluated its response to existing antimalarial drugs compared to that observed in humans. Immunocompromised BXN (
bg/bg xid/xid nu/nu
) mice were infected with either the sensitive NF54 strain or the multiresistant T24 strain and then treated with chloroquine, quinine, mefloquine, or dihydroartemisinin. A parallelism was observed between previously reported human responses and
P. falciparum
-parasitized human red blood cell (huRBC)–BXN mouse responses to classical antimalarial drugs, measured in terms of speed of decrease in parasitemia and of morphological alterations of the parasites. Mice infected with the sensitive strain were successfully cured after treatment with either chloroquine or mefloquine. In contrast, mice infected with the multiresistant strain failed to be cured by chloroquine or quinine but thereafter responded to dihydroartemisinin treatment. The speed of parasite clearance and the morphological alterations induced differed for each drug and matched previously reported observations, hence stressing the relevance of the model. These data thus suggest that
P. falciparum
-huRBC–BXN mice can provide a valuable in vivo system and should be included in the short list of animals that can be used for the evaluation of
P. falciparum
responses to drugs.
Differential C Isotope Discrimination by Fungi during Decomposition of C3- and C4-Derived Sucrose
Authors: Henn Matthew R. , Chapela Ignacio H. 
Published: July 2002

ABSTRACTStable isotope analysis is a major tool used in ecosystem studies to establish pathways and rates of C exchange between various ecosystem components. Little is known about isotopic effects of many such components, especially microbes. Here we report on the discovery of an unexpected pattern of C isotopic discrimination by basidiomycete fungi with far-reaching consequences for our understanding of isotopic processing in ecosystems where these microbes mediate material transfers across trophic levels. We measured fractionation effects on three ecologically relevant basidiomycete species under controlled laboratory conditions. Sucrose derived from C3and C4plants is fractionated differentially by these microbes in a taxon-specific manner. The differentiation between mycorrhizal and saprotrophic fungi observed in the field by others is not explained by intrinsic discrimination patterns. Fractionation occurs during sugar uptake and is sensitive to the nonrandom distribution of stable isotopes in the sucrose molecule. The balance between respiratory physiology and fermentative physiology modulates the degree of fractionation. These discoveries disprove the assumption that fungal C processing does not significantly alter the distribution of stable C isotopes and provide the basis for a reevaluation of ecosystem models based on isotopic evidence that involve C transfer across microbial interfaces. We provide a mechanism to account for the observed differential discrimination effects.
Biochemical and Genetic Characterization of Propionicin T1, a New Bacteriocin from
Propionibacterium thoenii
Authors: Faye Therese , Langsrud Thor , Nes Ingolf F. , Holo Helge 
Published: July 2002

ABSTRACT

A collection of propionibacteria was screened for bacteriocin production. A new bacteriocin named propionicin T1 was isolated from two strains of
Propionibacterium thoenii
. This bacteriocin shows no sequence similarity to other bacteriocins. Propionicin T1 was active against all strains of
Propionibacterium acidipropionici
,
Propionibacterium thoenii
, and
Propionibacterium jensenii
tested and also against
Lactobacillus sake
NCDO 2714 but showed no activity against
Propionibacterium freudenreichii
. The bacteriocin was purified, and the N-terminal part of the peptide was determined with amino acid sequencing. The corresponding gene
pctA
was sequenced, and this revealed that propionicin T1 is produced as a prebacteriocin of 96 amino acids with a typical
sec
leader, which is processed to give a mature bacteriocin of 65 amino acids. An open reading frame encoding a protein of 424 amino acids was found 68 nucleotides downstream the stop codon of
pctA
. The N-terminal part of this putative protein shows strong similarity with the ATP-binding cassette of prokaryotic and eukaryotic ABC transporters, and this protein may be involved in self-protection against propionicin T1. Propionicin T1 is the first bacteriocin from propionibacteria that has been isolated and further characterized at the molecular level.
Inhibitory Effects of Collagen on the PCR for Detection of
Clostridium perfringens
Authors: Kim Sangburm , Labbe Ronald G. , Ryu Sangryeol 
Published: July 2002

ABSTRACT

It is essential to identify specific food components that inhibit PCR in order to increase the sensitivity of the PCR method for rapid detection of pathogens contaminating a food. We found that collagen, a major component of several foods, inhibited PCR. The inhibitory action of collagen on PCR could be partially reversed by adjusting the concentration of magnesium ion in the reaction mixture and by the use of various DNA extraction methods to remove the collagen from the DNA. Also, the source of thermostable DNA polymerase was affected by the presence of collagen. These results suggest the need to optimize the extraction and assay conditions for rapid detection of enterotoxigenic
Clostridium perfringens
by PCR with respect to the kind of food being analyzed.
Rapid Methods for Testing the Efficacy of Sterilization-Grade Filter Membranes
Authors: Griffiths Matthew H. , Andrew Peter W. , Ball Peter R. , Hall George M. 
Published: July 2002

ABSTRACT

The validation of sterilization-grade membranes is integral to ensuring the efficient and safe use of microfiltration systems. Here validation refers to the production of sterile filtrate for sterilizing-grade membranes under challenge test conditions. Current validation methods require 48 h of culture for results to become available, which creates time delays within the manufacturing process and quality control (QC) backlogs. This work compares four methods for the production of filter challenge test data, to the desired test sensitivity, within 24 h using bioluminescent and fluorescent recombinant strains of the test organism
Brevundimonas diminuta
. These methods should provide a way to implement more rapid QC test regimens for filters.
Cloning of the
spoT
Gene of “
Candidatus
Phlomobacter fragariae” and Development of a PCR-Restriction Fragment Length Polymorphism Assay for Detection of the Bacterium in Insects
Authors: Foissac Xavier , Danet Jean-Luc , Zreik Leyla , Gandar Jeanne , Nourrisseau Jean-Georges , Bové Joseph-Marie , Garnier Monique 
Published: July 2002

ABSTRACT

Marginal chlorosis is a new disease of strawberry in which the uncultured phloem-restricted proteobacterium “
Candidatus
Phlomobacter fragariae” is involved. In order to identify the insect(s) vector(s) of this bacterium, homopteran insects have been captured. Because a PCR test based on the 16S rRNA gene (rDNA) applied to these insects was unable to discriminate between “P. fragariae” and other insect-associated proteobacteria, isolation of “P. fragariae” genes other than 16S rDNA was undertaken. Using comparative randomly amplified polymorphic DNAs, an amplicon was specifically amplified from “P. fragariae”-infected strawberry plants. It encodes part of a “P. fragariae” open reading frame sharing appreciable homology with the
spoT
gene from other proteobacteria. A
spoT
-based PCR test combined with restriction fragment length polymorphisms was developed and was able to distinguish “P. fragariae” from other insect bacteria. None of the many leafhoppers and psyllids captured during several years in and around infected strawberry fields was found to carry “P. fragariae.” Interestingly however, the “P. fragariae”
spoT
sequence could be easily detected in whiteflies proliferating on “P. fragariae”-infected strawberry plants under confined greenhouse conditions but not on control whiteflies, indicating that these insects can become infected with the bacterium.
Isolation of Mycobacteria from Frozen Fish Destined for Human Consumption
Authors: Mediel M. J. , Rodriguez V. , Codina G. , Martin-Casabona N. 
Published: July 2002

ABSTRACT

Mycobacteria were isolated from defrost water and tissue of sole (
Solea solea
), hake (
Merluccius merluccius
), cod (
Gadus morhua
), ling (
Genypterus blacodes
), and monkfish (
Lophius piscatorius
) on Löwenstein-Jensen medium after incubation at different temperatures. Samples of frozen fish were obtained under sterile conditions inside a refrigeration chamber (−18 to −22°C) in a wholesale market from which these products are distributed to shops for retail sale and human consumption.