bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of a Rabbit Model of Bacterial Endocarditis and an In Vitro Infection Model with Simulated Endocardial Vegetations
Authors: Hershberger Ellie , Coyle Elizabeth A. , Kaatz Glenn W. , Zervos Marcus J. , Rybak Michael J. 
Published: July 2002

ABSTRACT

Animal models are commonly used to determine the efficacy of various antimicrobial agents for treatment of bacterial endocarditis. Previously we have utilized an in vitro infection model, which incorporates simulated endocardial vegetations (SEVs) to evaluate the pharmacodynamics of various antibiotics. In the present study, we compared four experimental rabbit endocarditis protocols to an in vitro infection model in an effort to determine if these models are comparable. We have evaluated the activity of clinafloxacin, trovafloxacin, sparfloxacin, and ciprofloxacin in rabbit models against
Staphylococcus aureus
and
Enterococcus
spp. In vitro models were performed simulating the antibiotic pharmacokinetics obtained in the in vivo studies. Models were dosed the same as rabbit models, and SEVs were evaluated at the same time the rabbit vegetations were examined. Clinafloxacin and trovafloxacin were evaluated against methicillin-susceptible (MSSA1199) and -resistant (MRSA494) strains of
S. aureus
. Ciprofloxacin was studied against MSSA1199 and MSSA487. Sparfloxacin and clinafloxacin were evaluated against
Enterococcus faecium
SF2149 and
Enterococcus faecalis
WH245, respectively. We found that reductions in SEV bacterial density obtained in the in vitro model were similar to those obtained in rabbit vegetations, indicating that the SEV model may be a valuable tool for assessing antibiotic potential in the treatment of bacterial endocarditis.
Selection of Naturally Occurring Extended-Spectrum TEM β-Lactamase Variants by Fluctuating β-Lactam Pressure
Authors: Blazquez Jesús , Morosini María-Isabel , Negri María-Cristina , Baquero Fernando 
Published: July 2002

ABSTRACTDespite the large number of in vitro mutations that increase resistance to extended-spectrum cephalosporins in TEM-type β-lactamases, only a small number occur in naturally occurring enzymes. In nature, and particularly in the hospital, bacteria that contain β-lactamases encounter simultaneous or consecutive selective pressure with different β-lactam molecules. All variants obtained by submitting anEscherichia colistrain that contains ablaTEM-1gene to fluctuating challenge with both ceftazidime and amoxicillin contained only mutations previously detected in naturally occurring β-lactamases. Nevertheless, some variants obtained by ceftazidime challenge alone contained mutations never detected in naturally occurring TEM β-lactamases, suggesting that extended-spectrum TEM variants in hospital isolates result from fluctuating selective pressure with several β-lactams rather than selection with a single antibiotic.
Clearance of Infection withMycobacterium bovisBCG in Mice Is Enhanced by Treatment with S28463 (R-848), and Its Efficiency Depends on Expression of Wild-TypeNramp1(Resistance Allele)
Authors: Moisan Jacques , Wojciechowski Wojciech , Guilbault Claudine , Lachance Claude , Di Marco Sergio , Skamene Emil , Matlashewski Greg , Radzioch Danuta 
Published: July 2002

ABSTRACTThe mousebcghost resistance gene is known to control the activation of host macrophages for killing of intracellular parasites likeLeishmania donovanias well as intracellular bacteria, includingMycobacterium bovisBCG andSalmonella entericaserovar Typhimurium. TheNramp1gene has been mapped to this locus and affects the efficiency of macrophage activation. It has been shown that imidazoquinoline compounds, including S28463, are able to improve the clearance of a number of intracellular pathogens such as herpes simplex virus 2, human papillomavirus, andLeishmania. The goal of this study was to determine whether S28463 is efficient against infection with another intracellular pathogen,M. bovisBCG, and to determine the molecular basis underlying this effect. To achieve this, B10A.Nramp1rand B10A.Nramp1−/−mice were infected withM. bovisBCG and treated with S28463. The bacterial content in the spleen from these mice was assayed by a colony-forming assay. In addition, in vitro experiments were performed using bone marrow-derived macrophage cell lines from these mice. These cells were treated with S28463 and/or gamma interferon (IFN-γ), and nitric oxide (NO) production was measured. Our study was able to show that S28463 acts in synergy with IFN-γ to increase the production of NO in vitro. We were also able to demonstrate that mice that carried the resistant allele of theNramp1gene and were infected withM. bovisBCG responded to treatment with S28463, resulting in a decreased bacterial load after 2 weeks of treatment. Mice that do not express theNramp1gene responded only to a very large dose of S28463, and the response was not as efficient as that observed in mice carrying a wild-typeNramp1allele. Our data provide evidence for the potential of S28463 as an immunomodulator that may be helpful in designing efficient strategies to improve host defense against mycobacterial infection.
Characterization of OXA-29 fromLegionella(Fluoribacter)gormanii: Molecular Class D β-Lactamase with Unusual Properties
Authors: Franceschini Nicola , Boschi Letizia , Pollini Simona , Herman Raphaël , Perilli Mariagrazia , Galleni Moreno , Frère Jean-Marie , Amicosante Gianfranco , Rossolini Gian Maria 
Published: July 2002

ABSTRACTA class D β-lactamase determinant was isolated from the genome ofLegionella(Fluoribacter)gormaniiATCC 33297T. The enzyme, named OXA-29, is quite divergent from other class D β-lactamases, being more similar (33 to 43% amino acid identity) to those of groups III (OXA-1) and IV (OXA-9, OXA-12, OXA-18, and OXA-22) than to other class D enzymes (21 to 24% sequence identity). Phylogenetic analysis confirmed the closer ancestry of OXA-29 with members of the former groups. The OXA-29 enzyme was purified from anEscherichia colistrain overexpressing the gene via a T7-based expression system by a single ion-exchange chromatography step onS-Sepharose. The mature enzyme consists of a 28.5-kDa polypeptide and exhibits an isoelectric pH of >9. Analysis of the kinetic parameters of OXA-29 revealed efficient activity (kcat/Kmratios of >105M−1· s−1) for several penam compounds (oxacillin, methicillin, penicillin G, ampicillin, carbenicillin, and piperacillin) and also for cefazolin and nitrocefin. Oxyimino cephalosporins and aztreonam were also hydrolyzed, although less efficiently (kcat/Kmratios of around 103M−1· s−1). Carbapenems were neither hydrolyzed nor inhibitory. OXA-29 was inhibited by BRL 42715 (50% inhibitory concentration [IC50], 0.44 μM) and by tazobactam (IC50, 3.2 μM), but not by clavulanate. It was also unusually resistant to chloride ions (IC50, >100 mM). Unlike OXA-10, OXA-29 was apparently found as a dimer both in diluted solutions and in the presence of EDTA. Its activity was either unaffected or inhibited by divalent cations. OXA-29 is a new class D β-lactamase that exhibits some unusual properties likely reflecting original structural and mechanistic features.
SJ-3366, a Unique and Highly Potent Nonnucleoside Reverse Transcriptase Inhibitor of Human Immunodeficiency Virus Type 1 (HIV-1) That Also Inhibits HIV-2
Authors: Buckheit Robert W. , Watson Karen , Fliakas-Boltz Valerie , Russell Julie , Loftus Tracy L. , Osterling Mark C. , Turpin Jim A. , Pallansch Luke A. , White E. Lucile , Lee J.-W. , Lee S.-H. , Oh J.-W. , Kwon H.-S. , Chung S.-G. , Cho E.-H. 
Published: July 2002

ABSTRACT

We have identified and characterized a potent new nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) that also is active against HIV-2 and which interferes with virus replication by two distinct mechanisms. 1-(3-Cyclopenten-1-yl)methyl-6-(3,5-dimethylbenzoyl)-5-ethyl-2,4-pyrimidinedione (SJ-3366) inhibits HIV-1 replication at concentrations of approximately 1 nM, with a therapeutic index of greater than 4 × 10
6
. The efficacy and toxicity of SJ-3366 are consistent when evaluated with established or fresh human cells, and the compound is equipotent against all strains of HIV-1 evaluated, including syncytium-inducing, non-syncytium-inducing, monocyte/macrophage-tropic, and subtype virus strains. Distinct from other members of the pharmacologic class of NNRTIs, SJ-3366 inhibited laboratory and clinical strains of HIV-2 at a concentration of approximately 150 nM, yielding a therapeutic index of approximately 20,000. Like most NNRTIs, the compound was less active when challenged with HIV-1 strains possessing the Y181C, K103N, and Y188C amino acid changes in the RT and selected for a virus with a Y181C amino acid change in the RT after five tissue culture passages in the presence of the compound. In combination anti-HIV assays with nucleoside and nonnucleoside RT and protease inhibitors, additive interactions occurred with all compounds tested with the exception of dideoxyinosine, with which a synergistic interaction was found. Biochemically, SJ-3366 exhibited a

K
i

value of 3.2 nM, with a mixed mechanism of inhibition against HIV-1 RT, but it did not inhibit HIV-2 RT. SJ-3366 also inhibited the entry of both HIV-1 and HIV-2 into target cells. On the basis of its therapeutic index and multiple mechanisms of anti-HIV action, SJ-3366 represents an exciting new compound for use in HIV-infected individuals.
Human Antibodies to Bacterial Superantigens and Their Ability To Inhibit T-Cell Activation and Lethality
Authors: LeClaire Ross D. , Bavari Sina 
Published: July 2002

ABSTRACTBacterial superantigens (BSAgs) cause massive stimulation of the immune system and are associated with various pathologies and diseases. To address the role of antibodies in protection against BSAgs, we screened the sera of 29 human volunteers for antibodies to the SAgs staphylococcal enterotoxin A (SEA), SEB, SEC1, and toxic shock syndrome toxin 1 (TSST-1). Although all volunteers had detectable levels of antibodies against SEB and SEC1, many (9 out of 29 volunteers) lacked detectable antibody to SEA or had minimal titers. Antibody titers to TSST-1 were well below those to SEB and SEC1, and three volunteers lacked detectable antibody to this BSAg. In addition, pooled immunoglobulin preparations obtained from different companies had antibody titers against SEs and TSST-1. There was a good correlation between antibody titers and inhibition of superantigenic effects of these toxins. Transfer of SEB-specific antibodies, obtained from pooled sera, suppressed in vitro T-cell proliferation and totally protected mice against SEB. These data suggest that the inhibitory activity of human sera was specific to antibodies directed against the toxins. Thus, it may be possible to counteract with specific antibodies BSAg-associated pathologies caused by stimulation of the immune system.
Antiviral Guanosine Analogs as Substrates for Deoxyguanosine Kinase: Implications for Chemotherapy
Authors: Sjöberg Anita Herrström , Wang Liya , Eriksson Staffan 
Published: July 2002

ABSTRACT

A highly active form of human recombinant deoxyguanosine kinase (dGK) phosphorylated purine nucleoside analogs active against cytomegalovirus, hepatitis B virus, and human immunodeficiency virus, such as penciclovir, 2′,3′-dideoxyguanosine and 3′-fluoro-2′,3′-dideoxyguanosine. The antiherpesvirus drug ganciclovir, which is also used in gene therapy, was a substrate for dGK, but with low efficiency. ATP and UTP were both good phosphate donors, with apparent

K
m

values of 6 and 4 μM and
V
max
values of 34 and 90 nmol of dGMP/mg of dGK/min, respectively. With a mixture of 5 mM ATP and 0.05 mM UTP, which represent physiologically relevant concentrations, the activities of dGK with ganciclovir and penciclovir was 1% and approximately 10%, respectively, of that with dGuo. The levels of dGK in different tissues were determined with a selective enzyme assay and the total activities per gram of tissues were similar in liver, brain, heart, and thymus extracts. The fact that the cellular dGK enzyme can phosphorylate antiviral guanosine analogs may help to explain the efficacies and side effects of several forms of chemotherapy.
Antibiotic Susceptibilities of
Salmonella enterica
Serovar Typhi and
S. enterica
Serovar Paratyphi A Isolated from Patients in Japan
Authors: Hirose Kenji , Tamura Kazumichi , Sagara Hiroko , Watanabe Haruo 
Published: July 2002

ABSTRACT

The antibiotic susceptibilities of 62 strains of
Salmonella enterica
serovar Typhi and 37 strains of
S. enterica
serovar Paratyphi A were investigated with 18 antibiotics. Eighteen
S. enterica
serovar Typhi isolates and five
S. enterica
serovar Paratyphi A isolates were resistant to one or more antimicrobial agents, among which 10
S. enterica
serovar Typhi isolates were nalidixic acid resistant and also showed decreased ciprofloxacin susceptibility.
Pharmacokinetics of Itraconazole Oral Solution in Neutropenic Children during Long-Term Prophylaxis
Authors: Schmitt Claudine , Perel Yves , Harousseau Jean-luc , Lemerle Sophie , Chwetzoff Elisabeth , le Moing Jean-Pierre , Levron Jean-Claude 
Published: July 2002

ABSTRACT
We investigated the pharmacokinetics and safety of an oral solution of itraconazole in two groups of neutropenic children stratified by age. Effective concentrations of itraconazole in plasma were reached quickly and maintained throughout treatment. The results indicate a trend toward higher concentrations of itraconazole in plasma in older children.
Treatment of Tuberculosis Using a Combination of Sustained-Release Rifampin-Loaded Microspheres and Oral Dosing with Isoniazid
Authors: Quenelle Debra C. , Winchester Gary A. , Staas Jay K. , Barrow Esther L. W. , Barrow William W. 
Published: July 2002

ABSTRACT

Previously, we reported on the use of rifampin-loaded microspheres to effectively treat
Mycobacterium tuberculosis
-infected macrophages and mice. Using similar biocompatible polymeric excipients of lactide and glycolide copolymers, we have increased the rifampin loading of small microsphere formulations (1 to 10 μm) by fourfold. Improved formulations were evaluated individually and in combination with oral regimens of isoniazid for the treatment of
Mycobacterium tuberculosis
H37Rv-infected mice. Groups (10 mice per group) consisted of mice that received (i) oral dosages of isoniazid (25 to 0.19 mg/kg of body weight/day), (ii) two intraperitoneal injections of rifampin-loaded microspheres on days 0 and 7, (iii) a combination of small rifampin-loaded microspheres on days 0 and 7 and isoniazid orally for 25 days (12.5 to 0.39 mg/kg/day), (iv) placebo injections, and (v) no treatment. Treatment with rifampin-loaded microspheres alone resulted in significant reductions in the numbers of CFU in the lungs and spleens by day 26. A bioassay revealed that plasma rifampin levels from the microspheres exceeded the MICs by more than twofold throughout the 26-day experimental period. Susceptibility testing demonstrated continued sensitivity to rifampin during the treatment period. Whereas isoniazid alone significantly reduced the numbers of CFU for dosages ranging from 12.5 to 1.56 mg/kg, combination therapy with rifampin-loaded microspheres increased the effective range to 0.39 mg/kg. In many cases, complete elimination of CFU was obtained with the combination therapy, something not achieved with most of the single therapies. These results demonstrate the ability to use small microsphere formulations alone to achieve significant results in a murine tuberculosis model and also the ability to use them safely in combination with another antimycobacterial agent.
In Vitro Activities of Daptomycin against 2,789 Clinical Isolates from 11 North American Medical Centers
Authors: Barry Arthur L. , Fuchs Peter C. , Brown Steven D. 
Published: July 2002

ABSTRACT
The in vitro activity of daptomycin is affected by the concentration of calcium cations in the test medium. Mueller-Hinton broth is currently adjusted to contain 10 to 12.5 mg of magnesium per liter and 20 to 25 mg of calcium per liter, but for testing of daptomycin, greater concentrations of calcium (50 mg/liter) are recommended to better resemble the normal concentration of ionized calcium in human serum. Two levels of calcium were used for broth microdilution tests of 2,789 recent clinical isolates of gram-positive bacterial pathogens. MICs of daptomycin were two- to fourfold lower when the broth contained additional calcium. For most species, however, the percentages of strains that were inhibited by 2.0 μg of daptomycin per ml were essentially identical with the two broth media. Enterococci were the important exception; i.e., 92% were inhibited when tested in calcium-supplemented broth but only 35% were inhibited by 2.0 μg/ml without the additional calcium. This type of information should be considered when selecting criteria for defining in vitro susceptibility to daptomycin.
Comparison of Hydrogen Peroxide Contact Lens Disinfection Systems and Solutions against
Acanthamoeba polyphaga
Authors: Hughes Reanne , Kilvington Simon 
Published: July 2002

ABSTRACT

Acanthamoeba
is a free-living amoeba causing a potentially blinding infection of the cornea. Contact lens wearers are most at risk and account for some 95% of cases. Hydrogen peroxide is used for contact lens disinfection due to its broad antimicrobial activity. Lenses must be neutralized before use to avoid pronounced stinging and possible corneal damage. Neutralization is achieved by adding a catalyst during the disinfection process (one-step) or afterwards (two-step). Here, the activities of commercial peroxide systems and individual solutions against trophozoites and cysts of
Acanthamoeba polyphaga
were compared. All disinfection systems were active against trophozoites, giving a ≥3-log (99.9%) kill within 1 h. Of the four one-step systems, only one showed some cysticidal activity, giving a 1.28 ± 0.41-log reduction. Both two-step systems were cysticidal, giving a ≥3-log kill at 4 h. All system peroxide solutions were cysticidal, giving a ≥3-log kill by 4 to 6 h. Variation in the cysticidal rate was observed with two solutions that gave a 1.8- to 2.1-log kill at 4 h compared with 3.0 to 4.0 for the rest (
P
< 0.05). No cysticidal activity was found with the peroxigen sodium perborate or the contact lens protein remover subtilisin A. Two-step systems are cysticidal providing contact times of at least 4 h are employed. Variation in cyst killing occurs between peroxide solutions, possibly due to formulation differences. One-step systems are less effective against
Acanthamoeba
cysts due to rapid peroxide neutralization. The cysticidal activity of one-step systems could be improved if neutralization rates were retarded.
Clarithromycin Resistance and Eradication of
Helicobacter pylori
in Children
Authors: Kalach N. , Benhamou P. H. , Campeotto F. , Bergeret M. , Dupont C. , Raymond J. 
Published: July 2002

ABSTRACT

Outcome of
Helicobacter pylori
infection was analyzed in 61 children treated with a triple therapy including clarithromycin. Bacterial eradication was obtained in all children with clarithromycin-susceptible strains but not in children with clarithromycin-resistant ones (
P
= 0.0001).
H. pylori
antimicrobial susceptibility is mandatory before choosing a treatment, and clarithromycin should be avoided in case of resistance.
Artemisinin Pharmacokinetics and Efficacy in Uncomplicated-Malaria Patients Treated with Two Different Dosage Regimens
Authors: Gordi Toufigh , Huong Dinh Xuan , Hai Trinh Ngoc , Nieu Nguyen Thi , Ashton Michael 
Published: July 2002

ABSTRACT

The immediate efficacies of two oral dosage regimens of artemisinin were investigated in 77 male and female adult Vietnamese falciparum malaria patients randomly assigned to treatment with either 500 mg of artemisinin daily for 5 days (group A;
n
= 40) or artemisinin at a dose of 100 mg per day for 2 days, with the dose increased to 250 mg per day for 2 consecutive days and with a final dose of 500 mg on the fifth day (group B;
n
= 37). Parasitemia was monitored every 4 h. The average parasite clearance time was longer in group B than in group A (means ± standard deviations, 50 ± 23 and 34 ± 14 h, respectively;
P
< 0.01). Artemisinin concentrations in saliva samples obtained on days 1 and 5 were quantified by high-performance liquid chromatography. The average oral clearance, based on saliva drug concentrations in group B patients, was twofold higher than that in group A patients on day 1 (
P
< 0.01), with no differences in drug half-lives (
P
= 0.40), indicating a saturable first-pass metabolism. Female patients had higher oral clearance values on day 1. Artemisinin's pharmacokinetic parameters were similar on day 5 in both groups, although a significant increase in oral clearance from day 1 to day 5 was evident. Thus, artemisinin exhibited both dose- and time-dependent pharmacokinetics. The escalating dose studied did not result in higher artemisinin concentrations toward the end of the treatment period.
Viral Impacts on Total Abundance and Clonal Composition of the Harmful Bloom-Forming Phytoplankton
Heterosigma akashiwo
Authors: Tarutani Kenji , Nagasaki Keizo , Yamaguchi Mineo 
Published: July 2002

ABSTRACT

Recent observations that viruses are very abundant and biologically active components in marine ecosystems suggest that they probably influence various biogeochemical and ecological processes. In this study, the population dynamics of the harmful bloom-forming phytoplankton
Heterosigma akashiwo
(Raphidophyceae) and the infectious
H. akashiwo
viruses (HaV) were monitored in Hiroshima Bay, Japan, from May to July 1998. Concurrently, a number of
H. akashiwo
and HaV clones were isolated, and their virus susceptibilities and host ranges were determined through laboratory cross-reactivity tests. A sudden decrease in cell density of
H. akashiwo
was accompanied by a drastic increase in the abundance of HaV, suggesting that viruses contributed greatly to the disintegration of the
H. akashiwo
bloom as mortality agents. Despite the large quantity of infectious HaV, however, a significant proportion of
H. akashiwo
cells survived after the bloom disintegration. The viral susceptibility of
H. akashiwo
isolates demonstrated that the majority of these surviving cells were resistant to most of the HaV clones, whereas resistant cells were a minor component during the bloom period. Moreover, these resistant cells were displaced by susceptible cells, presumably due to viral infection. These results demonstrated that the properties of dominant cells within the
H. akashiwo
population change during the period when a bloom is terminated by viral infection, suggesting that viruses also play an important role in determining the clonal composition and maintaining the clonal diversity of
H. akashiwo
populations. Therefore, our data indicate that viral infection influences the total abundance and the clonal composition of one host algal species, suggesting that viruses are an important component in quantitatively and qualitatively controlling phytoplankton populations in natural marine environments.