bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemifloxacin Is Effective in Experimental Pneumococcal Meningitis
Authors: Smirnov A. , Wellmer A. , Gerber J. , Maier K. , Henne S. , Nau R. 
Published: July 2002

ABSTRACT

In a rabbit model of
Streptococcus pneumoniae
meningitis, 5 mg of gemifloxacin mesylate (SB-265805) per kg/h reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as 10 mg of ceftriaxone per kg/h (Δlog CFU/ml/h ± standard deviation [SD], −0.25 ± 0.09 versus −0.38 ± 0.11; serum and CSF concentrations of gemifloxacin were 2.1 ± 1.4 mg/liter and 0.59 ± 0.38 mg/liter, respectively, at 24 h). Coadministration of 1 mg of dexamethasone per kg did not affect gemifloxacin serum and CSF levels (2.7 ± 1.4 mg/liter and 0.75 ± 0.34 mg/liter, respectively, at 24 h) or activity (Δlog CFU/ml/h ± SD, −0.26 ± 0.11).
Streptococcus gordonii
Strains Resistant to Fluorodeoxyuridine Contain Mutations in the Thymidine Kinase Gene and Are Deficient in Thymidine Kinase Activity
Authors: Franke C. A. , Bolman T. M. , Ottum S. A. , Jones K. F. , Hruby D. E. 
Published: July 2002

ABSTRACT

Mutants of
Streptococcus gordonii
resistant to 5-fluorodeoxyuridine (FUdR
r
) were isolated. Each strain contained a point mutation resulting in the premature termination of the thymidine kinase (TK) open reading frame (
tdk
). In vitro translation of the mutant
tdk
coding regions resulted in synthesis of truncated TK polypeptides deficient in TK activity.
Consequences of VanE-Type Resistance on Efficacy of Glycopeptides In Vitro and in Experimental Endocarditis Due to
Enterococcus faecalis
Authors: Lafaurie Matthieu , Perichon Bruno , Lefort Agnes , Carbon Claude , Courvalin Patrice , Fantin Bruno 
Published: July 2002

ABSTRACT

The consequences on glycopeptide activity of low-level resistance to vancomycin due to VanE-type resistance were evaluated in vitro and in experimental endocarditis caused by
Enterococcus faecalis
BM4405 (MICs of vancomycin and teicoplanin: 16 and 0.5 μg/ml, respectively), its susceptible derivative BM4405-1, and susceptible
E. faecalis
JH2-2. After 24 h of incubation, vancomycin at 8 μg/ml was not active against
E. faecalis
BM4405 whereas it was bacteriostatic against strains BM4405-1 and JH2-2. Against all three strains, vancomycin at 30 μg/ml and teicoplanin at 8 or 30 μg/ml were bacteriostatic but bactericidal when combined with gentamicin. In rabbits with aortic endocarditis due to VanE-type resistant strain BM4405, treatment with a standard dose of vancomycin generated subinhibitory plasma concentrations (i.e., peak of 36.3 ± 2.1 μg/ml and trough of 6.0 ± 2.2 μg/ml) and led to no significant reduction in mean aortic valve vegetation counts compared to no treatment of control animals. In contrast, a higher dosing regimen of vancomycin (i.e., resulting in a peak of 38.3 ± 5.2 μg/ml and a trough of 15.0 ± 8.3 μg/ml), providing plasma concentrations above the MIC for the entire dosing interval, led to significant and similar activities against all three strains, which were enhanced by combination with gentamicin. Treatment with teicoplanin led to results similar to those obtained with vancomycin at a high dose. No subpopulations with increased resistance to glycopeptides were selected in vitro or in vivo. In conclusion, the use of a high dose of vancomycin was necessary for the treatment of experimental enterococcal endocarditis due to VanE-type strains.
In Vivo Efficacy of Telithromycin (HMR3647) against
Streptococcus pneumoniae
and
Haemophilus influenzae
Authors: Okamoto Hiroki , Miyazaki Shuichi , Tateda Kazuhiro , Ishii Yoshikazu , Yamaguchi Keizo 
Published: July 2002

ABSTRACT

The in vivo activity of telithromycin against erythromycin A- and penicillin G-resistant
Streptococcus pneumoniae
was superior to that of azithromycin, clarithromycin, cefdinir, and levofloxacin. In respiratory tract infections caused by erythromycin A-susceptible
S. pneumoniae
or
Haemophilus influenzae
in mice, telithromycin was more effective than clarithromycin and comparable to azithromycin.
In Vitro Activities and Postantifungal Effects of the Potent Dolastatin 10 Derivative Auristatin PHE
Authors: Woyke Tanja , Pettit George R. , Winkelmann Günther , Pettit Robin K. 
Published: July 2002

ABSTRACT

The pentapeptide dolavaline-valine-dolaisoleuine-dolaproine-phenylalanine-methyl ester (auristatin PHE) is a derivative of the anticancer drug dolastatin 10 (dolavaline-valine-dolaisoleuine-dolaproine-dolaphenine). Broth microdilution assays with a wide variety of yeast and filamentous fungal species demonstrated the specificity of auristatin PHE for
Cryptococcus neoformans
and several species of
Trichosporon
. The duration of the postantifungal effect (PAFE) for
C. neoformans
was determined for exposure times ranging from 30 min to 2 h. For the derivative, a PAFE was detectable after 45 min of exposure. The effect plateaued after 1 h of exposure, with a PAFE of approximately 6.5 h at four or eight times the auristatin PHE MIC. In contrast, there was no measurable PAFE after 1 h of exposure to dolastatin 10. Human serum greatly prolonged the PAFE of auristatin PHE at eight times the MIC. Auristatin PHE arrested
C. neoformans
in the budding stage, possibly due to a tubulin-inhibitory action. Auristatin PHE has potential as a narrow-spectrum fungicidal agent and as a probe that can be used to study cryptococcal cell division.
Emergence of Multiple Human Cytomegalovirus Ganciclovir-Resistant Mutants with Deletions and Substitutions within the UL97 Gene in a Patient with Severe Combined Immunodeficiency
Authors: Wolf Dana G. , Yaniv Isaac , Ashkenazi Shai , Honigman Alik 
Published: July 2002

ABSTRACT
Infection with multiple ganciclovir-resistant human cytomegalovirus mutants, containing different substitutions and deletions in the UL97 gene, was found in a patient with severe combined immunodeficiency (SCID) within 3 weeks of ganciclovir therapy. A novel 11-codon deletion at positions 590 to 600 was identified. These unique findings may be related to the nature of the immunodeficiency in the SCID patient.
In Vitro Activities of RWJ-54428 (MC-02,479) against Multiresistant Gram-Positive Bacteria
Authors: Chamberland Suzanne , Blais Johanne , Hoang Monica , Dinh Cynthia , Cotter Dylan , Bond Emmett , Gannon Carla , Park Craig , Malouin Francois , Dudley Michael N. 
Published: July 2002

ABSTRACT

RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity against gram-positive bacteria. In a broth microdilution susceptibility test against methicillin-resistant
Staphylococcus aureus
(MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC
90
) of 2 μg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIC
90
of 2 μg/ml. RWJ-54428 was active against
S. aureus, Staphylococcus epidermidis
, and
Staphylococcus haemolyticus
isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, ≤0.0625 to 1 μg/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible
S. aureus
(MIC
90
, 0.5 μg/ml). For ampicillin-susceptible
Enterococcus faecalis
(including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIC
90
of 0.125 μg/ml. RWJ-54428 was also active against
Enterococcus faecium
, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains. The potency against enterococci correlated with ampicillin susceptibility; RWJ-54428 MICs ranged between ≤0.0625 and 1 μg/ml for ampicillin-susceptible strains and 0.125 and 8 μg/ml for ampicillin-resistant strains. RWJ-54428 was more active than penicillin G and cefotaxime against penicillin-resistant, -intermediate, and -susceptible strains of
Streptococcus pneumoniae
(MIC
90
s, 0.25, 0.125, and ≤0.0625 μg/ml, respectively). RWJ-54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against
Haemophilus influenzae
and
Moraxella catarrhalis
(MIC
90
s, 0.25 and 0.5 μg/ml, respectively). This survey of the susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to RWJ-54428 indicates that this new cephalosporin has the potential to be useful in the treatment of infections due to gram-positive bacteria, including strains resistant to currently available antimicrobials.
In Vivo Efficacy of the New Ketolide Telithromycin (HMR 3647) in Murine Infection Models
Authors: Bonnefoy Alain , Guitton Michele , Delachaume Carole , Le Priol Pascal , Girard Anne-Marie 
Published: July 2002

ABSTRACT

We compared the oral antibacterial activities of telithromycin (HMR 3647), a new ketolide drug, in different infections induced in mice by
Staphylococcus aureus, Streptococcus pneumoniae
, streptococci, enterococci, and
Haemophilus influenzae
with those of various macrolides and pristinamycin. Unlike all other comparators, telithromycin displayed a high therapeutic activity, particularly in septicemia induced by erythromycin A-resistant pathogens, where the ketolide was the only active compound, displaying effective doses between 3 and 26 mg/kg of body weight. Against
H. influenzae,
telithromycin was the most effective compound. Telithromycin displayed bacteriostatic behavior against
S. pneumoniae
and
H. influenzae
. The ketolide was also active against thigh muscle infection induced by
S. aureus
. The pharmacokinetic properties of telithromycin accounted for its outstanding well-balanced oral in vivo efficacy against both gram-positive cocci, whatever their phenotype of resistance, and
H. influenzae
.
Effects of Synthetic Cecropin Analogs on in Vitro Growth of
Acholeplasma laidlawii
Authors: Borth Wayne B. , Jones V. P. , Ullman D. E. , Hu J. S. 
Published: July 2002

ABSTRACT

Four synthetic peptides (Peptidyl MIMs; Demeter Biotechnologies, Inc.) were evaluated for their in vitro activity against
Acholeplasma laidlawii
. Fifty percent effective concentration values ranged from 1 to 15 μM. Three of these compounds are more lethal than cecropin B against
A. laidlawii
.
Comparative In Vitro Activities of Gemifloxacin, Other Quinolones, and Nonquinolone Antimicrobials against Obligately Anaerobic Bacteria
Authors: Kleinkauf Niels , Ackermann Grit , Schaumann Reiner , Rodloff Arne C. 
Published: July 2002

ABSTRACT

The in vitro activity of gemifloxacin was compared to that of other quinolone and nonquinolone antimicrobials against 204 anaerobes by the agar dilution technique. The data indicate that gemifloxacin has a rather selective anaerobic activity. Most
Peptostreptococcus, Porphyromonas
, and
Fusobacterium
species are susceptible, while gemifloxacin's activity against other gram-negative anaerobes appears to be variable.
Induction of Epstein-Barr Virus Kinases To Sensitize Tumor Cells to Nucleoside Analogues
Authors: Moore Stacy M. , Cannon Jennifer S. , Tanhehco Yvette C. , Hamzeh Fayez M. , Ambinder Richard F. 
Published: July 2002

ABSTRACT

The presence of Epstein-Barr virus (EBV) in the tumor cells of some EBV-associated malignancies may facilitate selective killing of these tumor cells. We show that treatment of an EBV
+
Burkitt's lymphoma cell line with 5-azacytidine led to a dose-dependent induction of EBV lytic antigen expression, including expression of the viral thymidine kinase (TK) and phosphotransferase (PT). Azacytidine treatment for 24 h modestly sensitized the cell line to all nucleosides tested. To better characterize EBV TK with regard to various nucleoside analogues, we expressed EBV TK in stable cell clones. Two EBV TK-expressing clones were moderately sensitive to high doses of acyclovir and penciclovir (PCV) (62.5 to 500 μM) and to lower doses of ganciclovir (GCV) and bromovinyldeoxyuridine (BVdU) (10 to 100 μM) compared to a control clone and were shown to phosphorylate GCV. Similar experiments in a transient overexpression system showed more killing of cells transfected with the EBV TK expression vector than of cells transfected with the control mutant vector (50 μM GCV for 4 days). A putative PT was also studied in the transient transfection system and appeared similar to the TK in phosphorylating GCV and conferring sensitivity to GCV, but not in BVdU- or PCV-mediated cell killing. Induction of EBV kinases in combination with agents such as GCV merits further evaluation as an alternative strategy to gene therapy for selective killing of EBV-infected cells.
In Vitro Activity of Gemifloxacin (SB-265805, LB20304a) against
Legionella pneumophila
and Its Pharmacokinetics in Guinea Pigs with
L. pneumophila
Pneumonia
Authors: Edelstein Paul H. , Shinzato Takashi , Doyle Edward , Edelstein Martha A. C. 
Published: July 2002

ABSTRACT

The activity of gemifloxacin against intracellular
Legionella pneumophila
and for the treatment of guinea pigs with
L. pneumophila
pneumonia was studied. Gemifloxacin, azithromycin, and levofloxacin (1 μg/ml) reduced bacterial counts of two
L. pneumophila
strains grown in guinea pig alveolar macrophages by 2 to 3 log
10
units. Gemifloxacin and levofloxacin had roughly equivalent intracellular activities. In contrast, erythromycin had static activity only. Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in guinea pigs with
L. pneumophila
pneumonia. When gemifloxacin (10 mg/kg) was given by the intraperitoneal (i.p.) route to infected guinea pigs, mean peak levels in plasma were 1.3 μg/ml at 0.5 h and 1.2 μg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.3 h, and the area under the concentration-time curve from 0 to 24 h (AUC
0–24
) was 2.1 μg · h/ml. For the same drug dose, mean levels in lungs were 3.4 μg/g at both 0.5 and 1 h, with a half-life of 1.5 h and an AUC
0–24
of 6.0 μg · h/ml. All 15
L. pneumophila
-infected guinea pigs treated with gemifloxacin (10 mg/kg/dose given i.p. once daily) for 2 days survived for 9 days after antimicrobial therapy, as did 13 of 14 guinea pigs treated with the same dose of gemifloxacin given for 5 days. All 12 azithromycin-treated animals (15 mg/kg/dose given i.p. once daily for 2 days) survived, as did 11 of 12 animals treated with levofloxacin (10 mg/kg/dose given i.p. once daily for 5 days). None of 12 animals treated with saline survived. Gemifloxacin is effective against
L. pneumophila
in infected macrophages and in a guinea pig model of Legionnaires' disease, even with an abbreviated course of therapy. These data support studies of the clinical effectiveness of gemifloxacin for the treatment of Legionnaires' disease.
Intravenous Infusion of Cereport Increases Uptake and Efficacy of Acyclovir in Herpes Simplex Virus-Infected Rat Brains
Authors: Bidanset Deborah J. , Placidi Laurent , Rybak Rachel , Palmer Joyce , Sommadossi Jean-Pierre , Kern Earl R. 
Published: July 2002

ABSTRACT

The outcome of herpes simplex virus (HSV) infections manifesting as encephalitis in healthy or immunocompromised individuals is generally very poor with mortality rates of about 8 to 28% with treatment. The long-term prognosis of survivors is often problematic, posing the need for alternative treatments that may decrease the mortality and morbidity associated with herpes encephalitis. This study addresses one such approach that includes a temporary permeabilization of the blood-brain barrier during treatment with acyclovir (ACV). In these studies we utilized a synthetic bradykinin analog, Cereport (RMP-7), in conjunction with ACV to treat HSV infection of the brain in a rat model. Cereport, infused intravenously via the jugular vein, was shown to increase [
14
C]ACV uptake in both the HSV-1-infected and -uninfected rat brain by approximately two- to threefold, correlating with enhanced efficacy of ACV in various brain compartments. In another series of experiments to determine efficacy, various doses of unlabeled ACV were administered during infusion with RMP-7. The decrease in viral titers in the temporal regions of the brain after 5 days of treatment suggested that this approach enhanced the efficacy of ACV treatment. These data indicated that Cereport infused with ACV enhances both the penetration and efficacy of this drug in the treatment of an experimental HSV-1 infection of the rat brain.
In Vitro Activities of ABT-773, a New Ketolide, against Aerobic and Anaerobic Pathogens Isolated from Antral Sinus Puncture Specimens from Patients with Sinusitis
Authors: Goldstein Ellie J. C. , Conrads Georg , Citron Diane M. , Merriam C. Vreni , Warren Yumi , Tyrrell Kerin 
Published: July 2002

ABSTRACT

The comparative in vitro activities of ABT-773 against 207 aerobic and 162 anaerobic antral sinus puncture isolates showed that erythromycin-resistant pneumococcal strains were susceptible to ABT-773 (≤0.125 μg/ml); the MIC at which 90% of the isolates tested were inhibited for
Haemophilus influenzae
and other
Haemophilus
spp. was 4 μg/ml; and all
Moraxella
spp. and beta-lactamase-producing
Prevotella
species strains were inhibited by ≤0.125 μg/ml. Among the anaerobes tested, only fusobacteria (45%) required ≥4 μg of ABT-773/ml for inhibition. ABT-773 may offer a therapeutic alternative for sinus infections.
Antifungal Efficacy of Caspofungin (MK-0991) in Experimental Pulmonary Aspergillosis in Persistently Neutropenic Rabbits: Pharmacokinetics, Drug Disposition, and Relationship to Galactomannan Antigenemia
Authors: Petraitiene Ruta , Petraitis Vidmantas , Groll Andreas H. , Sein Tin , Schaufele Robert L. , Francesconi Andrea , Bacher John , Avila Nilo A. , Walsh Thomas J. 
Published: July 2002

ABSTRACT

The antifungal efficacy, pharmacokinetics, and safety of caspofungin (CAS) were investigated in the treatment and prophylaxis of invasive pulmonary aspergillosis due to
Aspergillus fumigatus
in persistently neutropenic rabbits. Antifungal therapy consisted of 1, 3, or 6 mg of CAS/kg of body weight/day (CAS1, CAS3, and CAS6, respectively) or 1 mg of deoxycholate amphotericin B (AMB)/kg/day intravenously for 12 days starting 24 h after endotracheal inoculation. Prophylaxis (CAS1) was initiated 4 days before endotracheal inoculation. Rabbits treated with CAS had significant improvement in survival and reduction in organism-mediated pulmonary injury (OMPI) measured by pulmonary infarct score and total lung weight (
P
< 0.01). However, animals treated with CAS demonstrated a paradoxical trend toward increased residual fungal burden (log CFU per gram) and increased serum galactomannan antigen index (GMI) despite improved survival. Rabbits receiving prophylactic CAS1 also showed significant improvement in survival and reduction in OMPI (
P
< 0.01), but there was no effect on residual fungal burden. In vitro tetrazolium salt hyphal damage assays and histologic studies demonstrated that CAS had concentration- and dose-dependent effects on hyphal structural integrity. In parallel with a decline in GMI, AMB significantly reduced the pulmonary tissue burden of
A. fumigatus
(
P
≤ 0.01). The CAS1, CAS3, and CAS6 dose regimens demonstrated dose-proportional exposure and maintained drug levels in plasma above the MIC for the entire 24-h dosing interval at doses that were ≥3 mg/kg/day. As serial galactomannan antigen levels may be used for therapeutic monitoring, one should be aware that profoundly neutropenic patients receiving echinocandins for aspergillosis might have persistent galactomannan antigenemia despite clinical improvement. CAS improved survival, reduced pulmonary injury, and caused dose-dependent hyphal damage but with no reduction in residual fungal burden or galactomannan antigenemia in persistently neutropenic rabbits with invasive pulmonary aspergillosis.
Development of Enzymatic Assays for Quantification of Intracellular Lamivudine and Carbovir Triphosphate Levels in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Patients
Authors: Kewn Stephen , Hoggard Patrick G. , Sales Sean D. , Jones Kevin , Maher Bridget , Khoo Saye H. , Back David J. 
Published: July 2002

ABSTRACT

In this paper, we describe the development and use of enzymatic assays to determine intracellular lamivudine triphosphate (3TCTP) and carbovir triphosphate (CBVTP) concentrations in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-infected patients. The assays involve inhibition of HIV reverse transcriptase (RT), which normally incorporates radiolabeled deoxynucleoside triphosphates into a synthetic template primer. For the 3TCTP assay, a preincubation procedure was added whereby 3TCTP becomes incorporated before [
3
H]dCTP. At a 1:400 template primer dilution, control product formation was reduced by 88.0% with 0.8 pmol of 3TCTP. Standard 3TCTP inhibition curves were performed using this procedure. For the CBVTP assay, 0.1 pmol of CBVTP inhibited control product formation with and without the use of a preincubation step, so inhibition curves were constructed using both procedures. However, reduced template primer stability with assays using preincubation steps led to a single-incubation procedure being adopted for future studies. The presence of PBMC extracts interfered with the 3TCTP assay. However, this was overcome by the addition of CuSO
4
. PBMC extracts did not interfere with the CBVTP assay. Intracellular 3TCTP and CBVTP concentrations were determined in PBMCs from HIV-infected patients over 24 h or greater. Peak concentrations were obtained 6 to 8 h after dosing, and the half-lives of the anabolites suggested the possibility of once-daily dosing. These assays are currently being used for determination of 3TCTP and CBVTP concentrations in clinical studies.
Combination Therapy with Indolylquinoline Derivative and Sodium Antimony Gluconate Cures Established Visceral Leishmaniasis in Hamsters
Authors: Pal Chiranjib , Raha Mousumi , Basu Anirban , Roy Keshab Chandra , Gupta Anasuya , Ghosh Monidipa , Sahu Niranjan Prasad , Banerjee Sukdeb , Mandal Nirup Bikash , Bandyopadhyay Santu 
Published: July 2002

ABSTRACT

2-(2″-Dichloroacetamidobenzyl)-3-(3′-indolylquinoline), designated indolylquinoline derivative A, reduced the splenic and the liver parasite burdens by >93.0% in
Leishmania donovani
-infected hamsters, whereas sodium antimony gluconate (SAG) reduced the burdens approximately 80.0%. Complete clearance of parasitemia from the livers and spleens was noticed when infected animals received indolylquinoline derivative A plus SAG, suggesting that indolylquinoline derivative A has potential as a new agent for sole or conjunctive therapy for leishmaniasis.