bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clarithromycin-Resistant
Mycobacterium avium
Is Still Susceptible to Treatment with Clarithromycin and Is Virulent in Mice
Authors: Bermudez Luiz E. , Nash Kevin , Petrofsky Mary , Young Lowell S. , Inderlied Clark B. 
Published: July 2002

ABSTRACT

Resistance to clarithromycin in breakthrough
Mycobacterium avium
complex (MAC) isolates typically occurs 3 to 4 months after the initiation of monotherapy in bacteremic AIDS patients. It has been suggested that continuation of clarithromycin therapy still results in clinical and microbiological improvement. To study this paradox, C57BL/6 beige mice were infected with a clarithromycin-resistant (MIC, ≥128 μg/ml) strain of MAC 101 (CLA-R MAC 101) and treated with 200 mg of clarithromycin per kg of body weight/day alone or in combination with ethambutol (100 mg/kg/day) for 2 weeks. Mice infected with a clarithromycin-susceptible strain of MAC 101 had bacterial loads reduced by 90% in the liver and 91% in the spleen (
P
< 0.05, compared with the control). Clarithromycin treatment of CLA-R MAC 101 resulted in a 65% reduction of bacterial loads in the liver (
P
= 0.009) and a 71% reduction in the spleen (
P
= 0.009), compared with the results for the untreated control. CLA-R MAC 101 and MAC 101 (isogenic strains) had comparable growth rates in murine tissue, ruling out a loss of virulence of CLA-R MAC 101. Strains of MAC currently defined as macrolide resistant may still respond to treatment with an agent such as clarithromycin within infected tissues.
Efficacy of the Echinocandin Caspofungin against Disseminated Aspergillosis and Candidiasis in Cyclophosphamide-Induced Immunosuppressed Mice
Authors: Abruzzo George K. , Gill Charles J. , Flattery Amy M. , Kong Li , Leighton Claire , Smith Jeffrey G. , Pikounis V. Bill , Bartizal Ken , Rosen Hugh 
Published: July 2002

ABSTRACT

The in vivo efficacy of the echinocandin antifungal caspofungin acetate (caspofungin; MK-0991) was evaluated in models of disseminated aspergillosis and candidiasis in mice with cyclophosphamide (CY)-induced immunosuppression. Caspofungin is a 1,3-β-
d
-glucan synthesis inhibitor efficacious against a number of clinically relevant fungi including
Aspergillus
and
Candida
species. Models of CY-induced transient or chronic leukopenia were used with once daily administration of therapy initiated 24 h after microbial challenge. Caspofungin was effective in treating disseminated aspergillosis in mice that were transiently leukopenic (significant prolongation of survival at doses of ≥0.125 mg/kg of body weight and a 50% protective dose [PD
50
] of 0.245 mg/kg/day at 28 days after challenge) or chronically leukopenic (50 to 100% survival at doses of ≥0.5 mg/kg and PD
50
s ranging from 0.173 to 0.400 mg/kg/day). Caspofungin was effective in the treatment and sterilization of
Candida
infections in mice with transient leukopenia with a 99% effective dose based on reduction in log
10
CFU of
Candida albicans
/gram of kidneys of 0.119 mg/kg and 80 to 100% of the caspofungin-treated mice having sterile kidneys at caspofungin doses from 0.25 to 2.0 mg/kg. In
Candida
-infected mice with chronic leukopenia, caspofungin was effective at all dose levels tested (0.25 to 1.0 mg/kg), with the log
10
CFU of
C. albicans
/gram of kidneys of caspofungin-treated mice being significantly lower (>99% reduction) than that of sham-treated mice from day 4 to day 28 after challenge. Also, 70 to 100% of the caspofungin-treated, chronic leukopenic mice had sterile kidneys at caspofungin doses of 0.5 to 1.0 mg/kg from day 8 to 28 after challenge. Sterilization of
Candida
infections by caspofungin in the absence of host leukocytes provides compelling in vivo evidence for fungicidal activity against
C. albicans
. Further human clinical trials with caspofungin against serious fungal infections are in progress.
Animal Pharmacokinetics and Interspecies Scaling of Sordarin Derivatives following Intravenous Administration
Authors: Aviles P. , Pateman A. , San Roman R. , Guillén M. J. , Gómez De Las Heras F. , Gargallo-Viola D. 
Published: July 2002

ABSTRACT

Sordarin derivatives constitute a new group of synthetic antifungal agents that selectively inhibit fungal protein synthesis. They have demonstrated in vitro activity against the most important fungal pathogens, both yeast and filamentous. This new family of compounds has also shown in vivo activity against murine
Candida albicans, Histoplasma capsulatum
, and
Coccidioides immitis
experimental infections, as well as against
Pneumocystis carinii
pneumonia in rats. After intravenous dosing in animals, both the area under the concentration-time curve and the elimination half-life were highest in
Cynomolgus
monkeys, followed by those in rats, mice, and rabbits. The volume of distribution at steady state for sordarin derivatives was similar in all species tested. The clearance in rats and mice was higher than for other species. GM 237354, a sordarin derivative, was characterized by high serum protein binding in mouse, rat, and monkey serum (unbound fraction, ≤5%). An indirect evaluation of the effect of liver function upon the metabolism of this class of compounds has been made in animals with impaired liver function such as Gunn rats, as well as in allometric studies that showed better correlations of half-life to liver blood flow than to animal body weight. Linearity of the main pharmacokinetic parameters was demonstrated after intravenous dosing of the representative compound GM 193663 at 10 and 20 mg/kg of body weight in rats. Allometry was used to determine whether human pharmacokinetic parameters can be predicted from animal data by regression analysis against body weight and liver blood flow. All these results have demonstrated that the human pharmacokinetics of sordarin derivatives can be forecast from animal data.
Activities of Newer Fluoroquinolones against Ciprofloxacin-Resistant
Streptococcus pneumoniae
Authors: Coyle Elizabeth A. , Kaatz Glenn W. , Rybak Michael J. 
Published: July 2002

ABSTRACT

The incidence of ciprofloxacin resistance in
Streptococcus pneumoniae
is low but steadily increasing, which raises concerns regarding the clinical impact of potential cross-resistance with newer fluoroquinolones. To investigate this problem, we utilized an in vitro pharmacodynamic model and compared the activities of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin to that of ciprofloxacin against two laboratory-derived, ciprofloxacin-resistant derivatives of
S. pneumoniae
(strains R919 and R921). Ciprofloxacin resistance in these strains involved the activity of a multidrug efflux pump and possibly, for R919, a mutation resulting in an amino acid substitution in GyrA. Gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin achieved 99.9% killing of both R919 and R921 in ≤28 h. With respect to levofloxacin, significant regrowth of both mutants was observed at 48 h (
P
< 0.05). For gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin, regrowth was minimal at 48 h, with each maintaining 99.9% killing against both mutants. No killing of either R919 or R921 was observed with exposure to ciprofloxacin. During model experiments, resistance to gatifloxacin, grepafloxacin, moxifloxacin, and trovafloxacin did not develop but the MICs of ciprofloxacin and levofloxacin increased 1 to 2 dilutions for both R919 and R921. Although specific area under the concentration-time curve from 0 to 24 h (AUC
0–24
)/MIC and maximum concentration of drug in serum (
C
max
)/MIC ratios have not been defined for the fluoroquinolones with respect to gram-positive organisms, our study revealed that significant regrowth and/or resistance was associated with AUC
0–24
/MIC ratios of ≤31.7 and
C
max
/MIC ratios of ≤3.1. It is evident that the newer fluoroquinolones tested possess improved activity against
S. pneumoniae
, including strains for which ciprofloxacin MICs were elevated.
In Vitro and In Vivo Activities of Syn2836, Syn2869, Syn2903, and Syn2921: New Series of Triazole Antifungal Agents
Authors: Salama S. M. , Atwal H. , Gandhi A. , Simon J. , Poglod M. , Montaseri H. , Khan J. K. , Furukawa T. , Saito H. , Nishida K. , Higashitani F. , Uji T. , Unemi N. , Daneshtalab M. , Micetich R. G. 
Published: July 2002

ABSTRACT

The in vitro and in vivo activities of four azole compounds belonging to a new series of 2(2,4-difluorophenyl)-3-(4-substituted piperazin-1-yl)-1-(1,2,4-triazol-1-yl) butanol antifungal agents is described. The compounds were selected from a library of azole compounds synthesized by our group. The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB). The MICs at which 90% of the isolates were inhibited (MIC
90
s) for the four test compounds for strains of
Candida
spp. ranged from <0.048 to 0.78 μg/ml. All compounds were also active against FLC-resistant
Candida albicans
and other
Candida
sp. strains. Moreover, MIC
90
s for strains of
Cryptococcus neoformans
,
Aspergillus
spp.,
Trichophyton
spp., and
Microsporum
spp. were also low and ranged from <0.048 to 0.39 μg/ml. The test compounds produced a fungistatic pattern during the time-kill kinetic studies. In vivo studies indicated that all four test compounds have good efficacies against
C. albicans
in a murine systemic infection model and significantly improved the survival rates of the infected mice. The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC. The compounds were also evaluated against an
Aspergillus fumigatus
systemic infection. Syn2903 was also superior to ITC, whereas the efficacy data for the other compounds were similar to those for ITC. It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing.
Drug Interactions with Clinafloxacin
Authors: Randinitis Edward J. , Alvey Christine W. , Koup Jeffery R. , Rausch George , Abel Robert , Bron Nicola J. , Hounslow Neil J. , Vassos Artemios B. , Sedman Allen J. 
Published: July 2002

ABSTRACTMany fluoroquinolone antibiotics are inhibitors of cytochrome P450 enzyme systems and may produce potentially important drug interactions when administered with other drugs. Studies were conducted to determine the effect of clinafloxacin on the pharmacokinetics of theophylline, caffeine, warfarin, and phenytoin, as well as the effect of phenytoin on the pharmacokinetics of clinafloxacin. Concomitant administration of 200 or 400 mg of clinafloxacin reduces mean theophylline clearance by approximately 50 and 70%, respectively, and reduces mean caffeine clearance by 84%. (R)-Warfarin concentrations in plasma during clinafloxacin administration are 32% higher and (S)-warfarin concentrations do not change during clinafloxacin treatment. An observed late pharmacodynamic effect was most likely due to gut flora changes. Phenytoin has no effect on clinafloxacin pharmacokinetics, while phenytoin clearance is 15% lower during clinafloxacin administration.
Glutathione Derivatives Active against
Trypanosoma brucei rhodesiense
and
T.
brucei brucei
In Vitro
Authors: Daunes Sylvie , D'Silva Claudius 
Published: July 2002

ABSTRACT

Diesters based on
N
-benzyloxycarbonyl-
S
-(2,4-dinitrophenyl) GSH (CBzGSDNP) containing linear alcohols 3 to 9, branched alcohols 10 to 20, or heteroatom linear alcohols 21 to 25, were investigated as in vitro inhibitors of pathogenic parasites. Diesters 3 to 25 were better inhibitors of
Trypanosoma brucei rhodesiense
than of
T. brucei brucei
and had low cytotoxicities. The most active compound had a 50% effective dose (ED
50
) of 0.2 μM. A quantitative structure activity regression equation relating the log (1/ED
50
) versus the hydrophobicity parameter (log
P
), Taft's steric parameter (

E
s

), molecular weight (MW), and the WienI descriptor (
W
) was determined, and the species difference was found to be related to membrane penetration and steric effects.
Effects of Metronidazole, Tetracycline, and Bismuth-Metronidazole-Tetracycline Triple Therapy in the
Helicobacter pylori
SS1 Mouse Model after 1 Day of Dosing: Development of an
H. pylori
Lead Selection Model
Authors: Sizemore Christine F. , Quispe Joel D. , Amsler Karen M. , Modzelewski Todd C. , Merrill Jayson J. , Stevenson D. Andrew , Foster Lorie A. , Slee Andrew M. 
Published: July 2002

ABSTRACT

We evaluated the effect of optimized doses and dosing schedules of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline (BMT) triple therapy with only 1 day of dosing on
Helicobacter pylori
SS1 titers in a mouse model. A reduction of bacterial titers was observable with 22.5 and 112.5 mg of metronidazole per kg of body weight (as well as BMT) given twice daily and four times daily (QID). Two hundred milligrams of tetracycline per kilogram, given QID, resulted in only a slight reduction of
H. pylori
titers in the stomach. We argue that optimization of doses based on antimicrobial drug levels in the animal and shortened (1 or 2 days) drug administration can be used to facilitate early evaluation of putative anti-
H. pylori
drug candidates in lieu of using human doses and extended schedules (7 to 14 days), as can be deduced from the results seen with these antimicrobial agents.
Purification and Properties of an Enzyme Capable of Degrading the Sheath of
Sphaerotilus natans
Authors: Takeda Minoru , Iohara Keishi , Shinmaru Sachie , Suzuki Ichiro , Koizumi Jun-Ichi 
Published: July 2002

ABSTRACT

Microorganisms which can degrade and grow on the purified sheath of a sheathed bacterium
Sphaerotilus natans
were collected from soil and river water. Two bacterial strains were isolated from the soil and designated strains TB and TK. Both strains are rod shaped, negatively stained by gram staining, facultatively anaerobic, and formed ellipsoidal endospores. These characteristics suggested that the isolates belong to the genus
Paenibacillus
, according to Ash et al. (C. Ash, F. G. Priest, and M. D. Collins, Antonie Leeuwenhoek 64:253–260, 1993). Phylogenetic analysis based on the 16S rDNA supported this possibility. Purification of the sheath-degrading enzyme was carried out from the culture broth of strain TB. The molecular weight of the enzyme was calculated to be 78,000 and 50,000 by sodium dodecyl sulfate-polyacrylamide electrophoresis and gel filtration chromatography, respectively. Enzyme activity was optimized at pH 6.5 to 7.0 and 30 to 40°C. The reaction was accelerated by the addition of Mg
2+
, Ca
2+
, Fe
3+
, and iodoacetamide, whereas it was inhibited by the addition of Cu
2+
, Mn
2+
, and dithiothreitol. The enzyme acted on the polysaccharide moiety of the sheath, producing an oligosaccharide the size of which was between the sizes of maltopentaose and maltohexaose. As the reaction proceeded, the absorbance at 235 nm of the reaction mixture increased, suggesting the generation of unsaturated sugars. Incorporation of unsaturated sugars was also suggested by the thiobarbituric acid reaction. It is possible that the enzyme is not a hydrolytic enzyme but a kind of polysaccharide eliminase which acts on the basic polysaccharide.
PCR Use of Highly Conserved DNA Regions for Identification of
Sinorhizobium meliloti
Authors: Sánchez-Contreras María , Lloret Javier , Martín Marta , Villacieros Marta , Bonilla Ildefonso , Rivilla Rafael 
Published: July 2002

ABSTRACT

A PCR identification method in which four primers that recognize homologous conserved regions in the
Sinorhizobium meliloti
genome are used was developed and tested. The regions used for identification were the nodbox 4 locus, which is located in one of the symbiotic megaplasmids, and the
mucR
gene, which is located in the chromosome. The new method was used to establish a collection of
S. meliloti
strains from polluted soils.
Hydrogen Peroxide Sensitivity of Catechol-2,3-Dioxygenase: a Cautionary Note on Use of
xylE
Reporter Fusions under Aerobic Conditions
Authors: Hassett Daniel J. , Ochsner Urs A. , Groce Stephanie L. , Parvatiyar Kislay , Ma Ju-Fang , Lipscomb John D. 
Published: July 2002

ABSTRACT

Catechol-2,3-dioxygenase (C23O) of
Pseudomonas putida
, encoded by the
xylE
gene, was found to be sensitive to hydrogen peroxide (H
2
O
2
) when used as a reporter in gene fusion constructs. Exposure of
Pseudomonas aeruginosa katA
or
katA katB
mutants harboring
katA
- or
katB-lacZ
(encoding β-galactosidase) or -
xylE
fusion plasmids to H
2
O
2
stimulated β-galactosidase activity, while there was little or no detectable C23O activity in these strains. More than 95% of C23O activity was lost after a 5-min exposure to equimolar H
2
O
2
, while a 10,000-fold excess was required for similar inhibition of β-galactosidase. Electron paramagnetic resonance spectra of the nitrosyl complexes of C23O showed that H
2
O
2
nearly stoichiometrically oxidized the essential active-site ferrous ion, thus accounting for the loss of activity. Our results suggest using caution in interpreting data derived from
xylE
reporter fusions under aerobic conditions, especially where oxidative stress is present or when catalase-deficient strains are used.
Ectomycorrhizal Fungal Associates of
Pinus contorta
in Soils Associated with a Hot Spring in Norris Geyser Basin, Yellowstone National Park, Wyoming
Authors: Cullings Ken , Makhija Shilpa 
Published: July 2002

ABSTRACT

Molecular methods and comparisons of fruiting patterns (i.e., presence or absence of fungal fruiting bodies in different soil types) were used to determine ectomycorrhizal (EM) associates of
Pinus contorta
in soils associated with a thermal soil classified as ultra-acidic to extremely acidic (pH 2 to 4). EM were sampled by obtaining 36 soil cores from six paired plots (three cores each) of both thermal soils and forest soils directly adjacent to the thermal area. Fruiting bodies (mushrooms) were collected for molecular identification and to compare fruiting body (above-ground) diversity to below-ground diversity. Our results indicate (i) that there were significant decreases in both the level of EM infection (130 ± 22 EM root tips/core in forest soil; 68 ± 22 EM root tips/core in thermal soil) and EM fungal species richness (4.0 ± 0.5 species/core in forest soil; 1.2 ± 0.2 species/core in thermal soil) in soils associated with the thermal feature; (ii) that the EM mycota of thermal soils was comprised of a small set of dominant species and included very few rare species, while the EM mycota of forest soils contained a few dominant species and several rare EM fungal species; (iii) that
Dermocybe phoenecius
and a species of
Inocybe
, which was rare in forest soils, were the dominant EM fungal species in thermal soils; (iv) that other than the single
Inocybe
species, there was no overlap in the EM fungal communities of the forest and thermal soils; and (v) that the fungal species forming the majority of the above-ground fruiting structures in thermal soils (
Pisolithus tinctorius
, which is commonly used in remediation of acid soils) was not detected on a single EM root tip in either type of soil. Thus,
P. tinctorius
may have a different role in these thermal soils. Our results suggest that this species may not perform well in remediation of all acid soils and that factors such as pH, soil temperature, and soil chemistry may interact to influence EM fungal community structure. In addition, we identified at least one new species with potential for use in remediation of hot acidic soil.
Purification and Characterization of the RecombinantThermussp. Strain T2 α-Galactosidase Expressed inEscherichia coli
Authors: Ishiguro Mitsunori , Kaneko Satoshi , Kuno Atsushi , Koyama Yoshinori , Yoshida Shigeki , Park Gwi-Gun , Sakakibara Yoshikiyo , Kusakabe Isao , Kobayashi Hideyuki 
Published: July 2002

ABSTRACTThe nucleotide sequence of theThermussp. strain T2 DNA coding for a thermostable α-galactosidase was determined. The deduced amino acid sequence of the enzyme predicts a polypeptide of 474 amino acids (Mr, 53,514). The observed homology between the deduced amino acid sequences of the enzyme and α-galactosidase fromThermus brockianuswas over 70%.Thermussp. strain T2 α-galactosidase was expressed in its active form inEscherichia coliand purified. Native polyacrylamide gel electrophoresis and gel filtration chromatography data suggest that the enzyme is octameric. The enzyme was most active at 75°C forp-nitrophenyl-α-d-galactopyranoside hydrolysis, and it retained 50% of its initial activity after 1 h of incubation at 70°C. The enzyme was extremely stable over a broad range of pH (pH 6 to 13) after treatment at 40°C for 1 h. The enzyme acted on the terminal α-galactosyl residue, not on the side chain residue, of the galactomanno-oligosaccharides as well as those of yeasts andMortierella vinaceaα-galactosidase I. The enzyme has only one Cys residue in the molecule.para-Chloromercuribenzoic acid completely inhibited the enzyme but did not affect the mutant enzyme which contained Ala instead of Cys, indicating that this Cys residue is not responsible for its catalytic function.
Isolation and Characterization of a Slowly Milk-Coagulating Variant of
Lactobacillus helveticus
Deficient in Purine Biosynthesis
Authors: Hebert Elvira M. , De Giori Graciela S. , Raya Raul R. 
Published: July 2002

ABSTRACT

A slowly milk-coagulating variant (Fmc
−
) of
Lactobacillus helveticus
CRL 1062, designated S1, was isolated and characterized. Strain S1 possessed all the known essential components required to utilize casein as a nitrogen source, which include functional proteinase and peptidase activities as well as functional amino acid, di- and tripeptide, and oligopeptide transport systems. The amino acid requirements of strain S1 were similar to those of the parental strain. However, on a purine-free, chemically defined medium, the growth rate of the Fmc
−
strain was threefold lower than that of the wild-type strain.
L. helveticus
S1 was found to be defective in IMP dehydrogenase activity and therefore was deficient in the ability to synthesize XMP and GMP. This conclusion was further supported by the observation that the addition of guanine or xanthine to milk, a substrate poor in purine compounds, restored the Fmc
+
phenotype of
L. helveticus
S1.
Microbial Growth on Dichlorobiphenyls Chlorinated on Both Rings as a Sole Carbon and Energy Source
Authors: Kim Sanggoo , Picardal Flynn 
Published: July 2002

ABSTRACT

We have isolated bacterial strains capable of aerobic growth on
ortho
-substituted dichlorobiphenyls as sole carbon and energy sources. During growth on 2,2′-dichlorobiphenyl and 2,4′-dichlorobiphenyl strain SK-4 produced stoichiometric amounts of 2-chlorobenzoate and 4-chlorobenzoate, respectively. Chlorobenzoates were not produced when strain SK-3 was grown on 2,4′-dichlorobiphenyl.