bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamics of Telavancin (TD-6424), a Novel Bactericidal Agent, against Gram-Positive Bacteria
Authors: Hegde Sharath S. , Reyes Noe , Wiens Tania , Vanasse Nicole , Skinner Robert , McCullough Julia , Kaniga Koné , Pace John , Thomas Roger , Shaw Jeng-Pyng , Obedencio Glen , Judice J. Kevin 
Published: July 2004

ABSTRACT

Telavancin (TD-6424) is a novel lipoglycopeptide that produces rapid and concentration-dependent killing of clinically relevant gram-positive organisms in vitro. The present studies evaluated the in vivo pharmacodynamics of telavancin in the mouse neutropenic thigh (MNT) and mouse subcutaneous infection (MSI) animal models. Pharmacokinetic-pharmacodynamic studies in the MNT model demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio was the best predictor of efficacy. Telavancin produced dose-dependent reduction of thigh titers of several organisms, including methicillin-susceptible
Staphylococcus aureus
(MSSA) and methicillin-resistant
Staphylococcus aureus
(MRSA), penicillin-susceptible and -resistant strains of
Streptococcus pneumoniae
, and vancomycin-resistant
Enterococcus faecalis
. The 50% effective dose (ED
50
) estimates for telavancin ranged from 0.5 to 6.6 mg/kg of body weight (administered intravenously), and titers were reduced by up to 3 log
10
CFU/g from pretreatment values. Against MRSA ATCC 33591, telavancin was 4- and 30-fold more potent (on an ED
50
basis) than vancomycin and linezolid, respectively. Against MSSA ATCC 13709, telavancin was 16- and 40-fold more potent than vancomycin and nafcillin, respectively. Telavancin, vancomycin, and linezolid were all efficacious and more potent against MRSA ATCC 33591 in the MSI model compared to the MNT model. This deviation in potency was, however, disproportionately greater for vancomycin and linezolid than for telavancin, suggesting that activity of telavancin is less affected by the immune status. The findings of these studies collectively suggest that once-daily dosing of telavancin may provide an effective approach for the treatment of clinically relevant infections with gram-positive organisms.
Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated with Increased Fluconazole Efficacy against Experimental Endocarditis Due to
Candida albicans
Authors: Yeaman Michael R. , Cheng Darwin , Desai Bhavesh , Kupferwasser Leon I. , Xiong Yan-Qiong , Gank Kimberly D. , Edwards John E. , Bayer Arnold S. 
Published: July 2004

ABSTRACT

Platelet microbicidal proteins (PMPs) are believed to be integral to host defense against endovascular infection. We previously demonstrated that susceptibility to thrombin-induced PMP 1 (tPMP-1) in vitro negatively influences
Candida albicans
virulence in the rabbit model of infective endocarditis (IE). This study evaluated the relationship between in vitro tPMP-1 susceptibility (tPMP-1
s
) or resistance (tPMP-1
r
) and efficacy of fluconazole (FLU) therapy of IE due to
C. albicans. Candida
IE was established in rabbits with either tPMP-1
s
or tPMP-1
r
strains. Treatment groups received FLU (100 mg/kg/day) intraperitoneally for 7 or 14 days; control animals received no therapy. At these time points, cardiac vegetations, kidneys, and spleens were quantitatively cultured to assess fungal burden. At both 7 and 14 days and in all target tissues, the extent of candidal clearance by FLU was greater in animals infected with the tPMP-1
s
strain than in those infected with the tPMP-1
r
strain. These differences were statistically significant in the spleen and kidney. Corroborating these in vivo data, FLU (a candidastatic agent), in combination with tPMP-1, exerted an enhanced fungicidal effect in vitro against tPMP-1
s
and tPMP-1
r
C. albicans
, with the extent of this effect greatest against the tPMP-1
s
strain. Collectively, these results support the concept that tPMP-1 susceptibility contributes to the net efficacy of FLU against
C. albicans
IE in vivo, particularly in tissues in which platelets and tPMP-1 likely play significant roles in host defense.
Emergence in Italy of a
Neisseria meningitidis
Clone with Decreased Susceptibility to Penicillin
Authors: Stefanelli Paola , Fazio Cecilia , Neri Arianna , Sofia Tonino , Mastrantonio Paola 
Published: July 2004

ABSTRACT

A rise in invasive diseases due to
Neisseria meningitidis
C:2b:P1.5 with decreased penicillin susceptibility occurred in Italy during the last 2 years. Real-time PCR identified the Pen
i
phenotype, and the
penA
sequence revealed the mosaicism of the gene. Molecular analyses assigned the isolates to a single emergent clone of the hypervirulent A4 cluster.
In Vitro Activities of Ravuconazole and Four Other Antifungal Agents against Fluconazole-Resistant or -Susceptible Clinical Yeast Isolates
Authors: Cuenca-Estrella Manuel , Gomez-Lopez Alicia , Mellado Emilia , Garcia-Effron Guillermo , Rodriguez-Tudela Juan L. 
Published: July 2004

ABSTRACT

The activities of ravuconazole and four other antifungal agents were tested against a collection of 1,796 clinical yeast isolates, including fluconazole-susceptible and -resistant strains. Ravuconazole was active against the majority of fluconazole-resistant isolates; but for 102 of 562 (18%) resistant isolates, mainly
Candida tropicalis
,
Candida glabrata
, and
Cryptococcus neoformans
, ravuconazole MICs were ≥1 μg/ml.
Omiganan Pentahydrochloride (MBI 226), a Topical 12-Amino-Acid Cationic Peptide: Spectrum of Antimicrobial Activity and Measurements of Bactericidal Activity
Authors: Sader Helio S. , Fedler Kelley A. , Rennie Robert P. , Stevens Shelley , Jones Ronald N. 
Published: July 2004

ABSTRACT
The activity of omiganan pentahydrochloride (formerly MBI 226; a synthetic cationic peptide) was assessed against 1,437 recent clinical bacterial isolates and 214 recent clinical yeast isolates. The omiganan was highly active, and minimal bactericidal concentrations or minimal fungicidal concentrations were either equal to or two- to fourfold higher than MICs. Kill curve experiments showed a clear pattern of bactericidal activity.
Inhibitory Activities of Colicins against
Escherichia coli
Strains Responsible for Postweaning Diarrhea and Edema Disease in Swine
Authors: Stahl Chad H. , Callaway Todd R. , Lincoln Leslie M. , Lonergan Steven M. , Genovese Kenneth J. 
Published: July 2004

ABSTRACT

The efficacies of colicins E1 and N against
Escherichia coli
strains responsible for postweaning diarrhea and edema disease, two of the most prevalent disease problems for pigs in the United States, were determined in vitro. These proteins may provide an environmentally sound means for the prevention of these infections in swine.
In Vitro Activity and Potency of an Intravenously Injected Antimicrobial Peptide and Its
dl
Amino Acid Analog in Mice Infected with Bacteria
Authors: Braunstein Amir , Papo Niv , Shai Yechiel 
Published: July 2004

ABSTRACT

We report that intravenous injection (3 mg/kg of body weight twice daily) of a diastereomer (containing 33%
d
amino acids) of an antimicrobial peptide, K
6
L
9
(LKLLKKLLKKLLKLL-NH
2
), but not the all-
l
-amino-acid parental peptide, cures neutropenic mice infected with gentamicin-sensitive
Pseudomonas aeruginosa
and gentamicin-resistant
Acinetobacter baumannii
bacteria. Various biophysical experiments suggest a membranolytic-like effect.
In Vitro Killing ofMycobacterium ulceransby Acidified Nitrite
Authors: Phillips R. , Kuijper S. , Benjamin N. , Wansbrough-Jones M. , Wilks M. , Kolk A. H. J. 
Published: July 2004

ABSTRACTMycobacterium ulcerans, which causes Buruli ulcer, was exposed to acidified nitrite or to acid alone for 10 or 20 min. Killing was rapid, and viable counts were reduced below detectable limits within 10 min of exposure to 40 mM acidified nitrite.M. ulceransis highly susceptible to acidified nitrite in vitro.
Lack of Activity of Orally Administered Clofazimine against IntracellularMycobacterium tuberculosisin Whole-Blood Culture
Authors: Janulionis Ernestas , Sofer Carolina , Song Ho-Yeon , Wallis Robert S. 
Published: July 2004

ABSTRACTThe activity of oral clofazimine against intracellularMycobacterium tuberculosiswas compared to that of ofloxacin in healthy volunteers by the use of whole-blood cultures. Clofazimine was inactive whether it was tested alone or combined with other drugs that are used to treat multidrug-resistant tuberculosis, despite a total dose of 2 g. Kanamycin was the most active drug tested.
Pharmacokinetics of Intravenous Itraconazole in Stable Hemodialysis Patients
Authors: Mohr John F. , Finkel Kevin W. , Rex John H. , Rodriguez Jose R. , Leitz Gerhard J. , Ostrosky-Zeichner Luis 
Published: July 2004

ABSTRACTThe pharmacokinetics of intravenous itraconazole (ITC) was studied in dialysis patients. Dialysis had no effect on the half-life and clearance of ITC or OH-ITC. However, dialysis allowed the clearance of hydroxypropyl-β-cyclodextrin (HP-β-CD). The area under the concentration-time curve from time zero to infinity (AUC0-∞) for HP-β-CD administered before dialysis was lower than the AUC0-∞when it was administered after dialysis (P< 0.01). Administration of ITC intravenously just prior to hemodialysis appears to produce adequate systemic exposures of ITC and OH-ITC while allowing dialysis clearance of HP-β-CD. Studies of multiple administrations are warranted.
Effect of Granulocyte Colony-Stimulating Factor Combination Therapy on Efficacy of Posaconazole (SCH56592) in an Inhalation Model of Murine Pulmonary Aspergillosis
Authors: Patera Andriani C. , Menzel Frederick , Jackson Craig , Brieland Joan K. , Halpern Judy , Hare Roberta , Cacciapuoti Anthony , Loebenberg David 
Published: July 2004

ABSTRACTUsing an inhalation model of pulmonary aspergillosis, we observed modest differences in the survival rates of mice treated with granulocyte colony-stimulating factor (G-CSF) and posaconazole (POS) and those treated with POS alone. This finding is in contrast to a previous report that suggested that G-CSF had a significant antagonistic effect on the antifungal activity of POS.
High Prevalence of Extended-Spectrum β-Lactamase-Producing Strains among Blood Isolates of
Enterobacter
spp. Collected in a Tertiary Hospital during an 8-Year Period and Their Antimicrobial Susceptibility Patterns
Authors: Pai Hyunjoo , Hong Jung Yun , Byeon Jeong-Hum , Kim Yun-Kyung , Lee Hoan-Jong 
Published: July 2004

ABSTRACT

Of 72 blood isolates of
Enterobacter
spp. collected over an 8-year period, 50% (36 of 72) were derepressed or partially derepressed AmpC mutants. The extended-spectrum β-lactamase (ESBL) production rate was 43% (31 of 72 isolates), and 67.3% (31 of 46) of extended-spectrum cephalosporin-resistant strains produced ESBLs. Thus, a confirmatory test for ESBL production is necessary for extended-spectrum cephalosporin-resistant
Enterobacter
spp.
Temporin A Soaking in Combination with Intraperitoneal Linezolid Prevents Vascular Graft Infection in a Subcutaneous Rat Pouch Model of Infection with
Staphylococcus epidermidis
with Intermediate Resistance to Glycopeptides
Authors: Giacometti Andrea , Cirioni Oscar , Ghiselli Roberto , Orlando Fiorenza , D'Amato Giuseppina , Kamysz Wojciech , Mocchegiani Federico , Sisti Valerio , Silvestri Carmela , Łukasiak Jerzy , Rocchi Marco , Saba Vittorio , Scalise Giorgio 
Published: July 2004

ABSTRACT

The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant
Staphylococcus epidermidis
with intermediate resistance to glycopeptides was investigated in a subcutaneous rat pouch model. Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs.
In Vitro Activities of Telithromycin, Linezolid, and Quinupristin-Dalfopristin against
Streptococcus pneumoniae
with Macrolide Resistance Due to Ribosomal Mutations
Authors: Farrell David J. , Morrissey Ian , Bakker Sarah , Buckridge Sylvie , Felmingham David 
Published: July 2004

ABSTRACT

To date, 86 of 7,746 macrolide-resistant
Streptococcus pneumoniae
isolates from 1999 to 2002 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance studies were negative for methylase and efflux mechanisms. Mutations in 23S rRNA or the genes encoding riboprotein L4 or L22 were found in 77 of 86 isolates. Six isolates were resistant to quinupristin-dalfopristin and two were resistant to linezolid, while telithromycin demonstrated good activities against all isolates.
CMY-13, a Novel Inducible Cephalosporinase Encoded by anEscherichia coliPlasmid
Authors: Miriagou V. , Tzouvelekis L. S. , Villa L. , Lebessi E. , Vatopoulos A. C. , Carattoli A. , Tzelepi E. 
Published: July 2004

ABSTRACTAn IncN plasmid (p541) fromEscherichia colicarried aCitrobacter freundii-derived sequence of 4,252 bp which included anampC-ampRregion and was bound by two directly repeated IS26elements.ampCencoded a novel cephalosporinase (CMY-13) with activity similar to that of CMY-2. AmpR was likely functional as indicated in induction experiments.
Remarkable Increase in Central Japan in 2001-2002 of
Neisseria gonorrhoeae
Isolates with Decreased Susceptibility to Penicillin, Tetracycline, Oral Cephalosporins, and Fluoroquinolones
Authors: Ito Masayasu , Yasuda Mitsuru , Yokoi Shigeaki , Ito Shin-ichi , Takahashi Yoshito , Ishihara Satoshi , Maeda Shin-ichi , Deguchi Takashi 
Published: July 2004

ABSTRACT

Four hundred sixty-two clinical isolates of
Neisseria gonorrhoeae
recovered from 1999 through 2002 in central Japan were examined for MICs of antimicrobial agents. The majority was sensitive to ceftriaxone and spectinomycin, but a remarkable increase in isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones was observed from 2001 through 2002.
Antianaerobic Activity of a Novel Fluoroquinolone, WCK 771, Compared to Those of Nine Other Agents
Authors: Peric Mihaela , Jacobs Michael R. , Appelbaum Peter C. 
Published: July 2004

ABSTRACT
Agar dilution MIC methodology was used to compare the activity of WCK 771 with those of ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin, piperacillin, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 350 anaerobes. Overall, the MICs (in micrograms per milliliter) at which 50 and 90%, respectively, of the isolates tested were inhibited were as follows: WCK 771, 0.5 and 2.0; ciprofloxacin, 2.0 and 32.0; levofloxacin, 1.0 and 8.0; gatifloxacin, 0.5 and 4.0; moxifloxacin, 0.5 and 4.0; piperacillin, 2.0 and 64.0; piperacillin-tazobactam, ≤0.125 and 8.0; imipenem, 0.125 and 1.0; clindamycin, 0.125 and 16.0; and metronidazole, 1.0 and >16.0.
Novel Antimalarial Compounds Isolated in a Survey of Self-Medicative Behavior of Wild Chimpanzees in Uganda
Authors: Krief Sabrina , Martin Marie-Thérèse , Grellier Philippe , Kasenene John , Sévenet Thierry 
Published: July 2004

ABSTRACT

Following a veterinary and behavioral survey of chimpanzees from a natural population in Uganda, leaf samples of
Trichilia rubescens
were collected because of the unusual method of ingestion observed. The methanolic crude extract of
T. rubescens
leaves exhibited significant antimalarial activity in vitro. Bioassay-directed fractionation provided two new limonoids, trichirubines A and B. A greater understanding of the role of secondary compounds in the primate diet may be helpful in recovering naturally occurring compounds of medicinal significance for human medicine.
Susceptibility of
Chlamydia trachomatis
to Excipients Commonly Used in Topical Microbicide Formulations
Authors: Lampe M. F. , Rohan L. C. , Skinner M. C. , Stamm W. E. 
Published: July 2004

ABSTRACT

Commonly used “inactive” pharmaceutical excipients were tested in a previously developed minimum cidal concentration assay to assess their ability to kill
Chlamydia trachomatis
topically. Sixteen excipients were evaluated in these studies under various conditions. A range of activities was found among the excipients that could be tested in our assay system.
Expression of Members of the 28-Kilodalton Major Outer Membrane Protein Family ofEhrlichia chaffeensisduring Persistent Infection
Authors: Zhang Jian-zhi , Guo Hong , Winslow Gary M. , Yu Xue-jie 
Published: July 2004

ABSTRACTThe 28-kDa immunodominant outer membrane proteins (P28 OMPs) ofEhrlichia chaffeensisare encoded by a multigene family. As an indirect measure of the in vivo expression of the members of thep28multigene family ofE. chaffeensis, sera from two beagle dogs experimentally infected withE. chaffeensiswere evaluated for the presence of specific antibodies to P28 OMPs by enzyme-linked immunosorbent assay. Antigenic peptides unique to each of the P28s were identified within the first hypervariable region of each P28 OMP. Serological responses to peptides derived from all P28 OMPs were detected from day 30 postinoculation to day 468 and from day 46 until day 159 in the two beagles. Although antibody titers to the peptides fluctuated, the peak response to all of the peptides appeared simultaneously in each dog. The antibody responses to another outer membrane protein ofE. chaffeensis(GP120) showed similar temporal and quantitative changes. These data suggest that the P28 OMPs are expressed concurrently during persistentEhrlichiainfection.
Cleavage of Human Transferrin by
Porphyromonas gingivalis
Gingipains Promotes Growth and Formation of Hydroxyl Radicals
Authors: Goulet Véronique , Britigan Bradley , Nakayama Koji , Grenier Daniel 
Published: July 2004

ABSTRACT

Porphyromonas gingivalis
, a gram-negative anaerobic bacterium associated with active lesions of chronic periodontitis, produces several proteinases which are presumably involved in host colonization, perturbation of the immune system, and tissue destruction. The aims of this study were to investigate the degradation of human transferrin by gingipain cysteine proteinases of
P. gingivalis
and to demonstrate the production of toxic hydroxyl radicals (HO
·
) catalyzed by the iron-containing transferrin fragments generated or by release of iron itself. Analysis by polyacrylamide gel electrophoresis and Western immunoblotting showed that preparations of Arg- and Lys-gingipains of
P. gingivalis
cleave transferrin (iron-free and iron-saturated forms) into fragments of various sizes. Interestingly, gingival crevicular fluid samples from diseased periodontal sites but not samples from healthy periodontal sites contained fragments of transferrin. By using
55
Fe-transferrin, it was found that degradation by
P. gingivalis
gingipains resulted in the production of free iron, as well as iron bound to lower-molecular-mass fragments. Subsequent to the degradation of transferrin, bacterial cells assimilated intracellularly the radiolabeled iron. Growth of
P. gingivalis
ATCC 33277, but not growth of an Arg-gingipain- and Lys-gingipain-deficient mutant, was possible in a chemically defined medium containing 30% iron-saturated transferrin as the only source of iron and peptides, suggesting that gingipains play a critical role in the acquisition of essential growth nutrients. Finally, the transferrin degradation products generated by Arg-gingipains A and B were capable of catalyzing the formation of HO
·
, as determined by a hypoxanthine/xanthine oxidase system and spin trapping-electron paramagnetic resonance spectrometry. Our study indicates that
P. gingivalis
gingipains degrade human transferrin, providing sources of iron and peptides. The iron-containing transferrin fragments or the release of iron itself may contribute to tissue destruction by catalyzing the formation of toxic HO
·
.
Intranasal Coadministration of the Cry1Ac Protoxin with Amoebal Lysates Increases Protection againstNaegleria fowleriMeningoencephalitis
Authors: Rojas-Hernández Saúl , Rodríguez-Monroy Marco A. , López-Revilla Rubén , Reséndiz-Albor Aldo A. , Moreno-Fierros Leticia 
Published: July 2004

ABSTRACTCry1Ac protoxin has potent mucosal and systemic adjuvant effects on antibody responses to proteins or polysaccharides. In this work, we examined whether Cry1Ac increased protective immunity against fatalNaegleria fowleriinfection in mice, which resembles human primary amoebic meningoencephalitis. Higher immunoglobulin G (IgG) than IgA anti-N. fowleriresponses were elicited in the serum and tracheopulmonary fluids of mice immunized by the intranasal or intraperitoneal route withN. fowlerilysates either alone or with Cry1Ac or cholera toxin. Superior protection against a lethal challenge with 5 × 104liveN. fowleritrophozoites was achieved for immunization by the intranasal route. Intranasal immunization ofN. fowlerilysates coadministered with Cry1Ac increased survival to 100%; interestingly, immunization with Cry1Ac alone conferred similar protection to that achieved with amoebal lysates alone (60%). When mice intranasally immunized with Cry1Ac plus lysates were challenged with amoebae, both IgG and IgA mucosal responses were rapidly increased, but only the increased IgG response persisted until day 60 in surviving mice. The brief rise in the level of specific mucosal IgA does not exclude the role that this isotype may play in the early defense against this parasite, since higher IgA responses were detected in nasal fluids of mice intranasally immunized with lysates plus either Cry1Ac or cholera toxin, which, indeed, were the treatments that provided the major protection levels. In contrast, serum antibody responses do not seem to be related to the protection level achieved. Both acquired and innate immune systems seem to play a role in host defense againstN. fowleriinfection, but further studies are required to elucidate the mechanisms involved in protective effects conferred by Cry1Ac, which may be a valuable tool to improve mucosal vaccines.
Sequence and Binding Activity of the Autolysin-Adhesin Ami from Epidemic
Listeria monocytogenes
4b
Authors: Milohanic Eliane , Jonquières Renaud , Glaser Philippe , Dehoux Pierre , Jacquet Christine , Berche Patrick , Cossart Pascale , Gaillard Jean-Louis 
Published: July 2004

ABSTRACT

Ami is an autolytic amidase from
Listeria monocytogenes
that is targeted to the bacterial surface via its C-terminal cell wall anchoring (CWA) domain. We recently showed that the CWA domain from Ami of
L. monocytogenes
EGD (serovar 1/2a) (Ami 1/2a) mediated bacterial binding to mammalian cells. Here we studied the sequence and binding properties of Ami from CHUT 82337 (serovar 4b) (Ami 4b). The Ami 4b polypeptide is predicted to be 770 amino acids long (compared with the 917 amino acids of Ami 1/2a from EGD). Ami 1/2a and Ami 4b are almost identical in the N-terminal enzymatic domain (∼98% amino acid identity), but the sequence is poorly conserved in the C-terminal CWA domain, with only ∼54% amino acid identity and eight GW modules in Ami 1/2a compared with six GW modules in Ami 4b. The purified Ami 4b CWA domain efficiently bound serovar 4b bacterial cells and only poorly bound serovar 1/2a bacterial cells. The Ami 4b CWA domain was also significantly less able to bind Hep-G2 human hepatocytic cells than the Ami 1/2a CWA domain. We sequenced the
ami
regions encoding CWA domains of reference strains belonging to the 12
L. monocytogenes
serovars. The phylogenic tree constructed from the sequences yielded a binary division into group I (serovars 1/2a, 1/2b, 1/2c, 3a, 3b, 3c, and 7) and group II (serovars 4a, 4b, 4c, 4d, and 4e). This is the first direct evidence of divergence between serovars 1/2a and 4b in a gene involved in the adhesion of
L. monocytogenes
to mammalian cells, as well as the first demonstration of allelic polymorphism correlated with the somatic antigen in this species.