bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiretroviral Agents Inhibit Infection of Human Cells by Porcine Endogenous Retroviruses
Authors: Powell S. K. , Gates M. E. , Langford G. , Gu M.-L. , Lockey C. , Long Z. , Otto E. 
Published: July 2002

ABSTRACT
The efficacy of antiretroviral drugs against porcine endogenous retroviruses (PERV) that may be harbored in pig organs intended for transplantation was examined in human cells in vitro. The nucleoside analogs zidovudine and dideoxyinosine were found to effectively inhibit PERV replication.
Effects of MS-8209, an Amphotericin B Derivative, on Tumor Necrosis Factor Alpha Synthesis and Human Immunodeficiency Virus Replication in Macrophages
Authors: Clayette Pascal , Martin Marc , Beringue Vincent , Dereuddre-Bosquet Nathalie , Adjou Karim T. , Seman Michel , Dormont Dominique 
Published: July 2002

ABSTRACT
Amphotericin B derivatives, such as MS-8209, have been evaluated as a therapeutic approach to human immunodeficiency virus (HIV) infection. We show that MS-8209, like amphotericin B, increases tumor necrosis factor alpha (TNF-α) mRNA expression and TNF-α production and consequently HIV replication in human macrophages. These effects confirm the pharmacological risk associated with the administration of amphotericin B or its derivatives to HIV-infected patients.
In Vitro Activity of A-192411.29, a Novel Antifungal Lipopeptide
Authors: Nilius Angela M. , Raney Patti M. , Hensey-Rudloff Dena M. , Wang Weibo , Li Qun , Flamm Robert K. 
Published: July 2002

ABSTRACT

A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as
Candida albicans
,
Candida tropicalis
, and
Candida glabrata
, as well as less commonly encountered
Candida
species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against
Candida
strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against
Cryptococcus neoformans
was comparable to its activity against
Candida
spp. However, A-192411.29 did not demonstrate complete growth inhibition of
Aspergillus fumigatus
by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.
In Vitro Selection of Mutations in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase That Decrease Susceptibility to (−)-β-
d
-Dioxolane-Guanosine and Suppress Resistance to 3′-Azido-3′-Deoxythymidine
Authors: Bazmi Holly Z. , Hammond Jennifer L. , Cavalcanti Socrates C. H. , Chu Chung K. , Schinazi Raymond F. , Mellors John W. 
Published: July 2002

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) isolates resistant to (−)-β-
d
-dioxolane-guanosine (DXG), a potent and selective nucleoside analog HIV-1 reverse transcriptase (RT) inhibitor, were selected by serial passage of HIV-1
LAI
in increasing drug concentrations (maximum concentration, 30 μM). Two independent selection experiments were performed. Viral isolates for which the DXG median effective concentrations (EC
50
s) increased 7.3- and 12.2-fold were isolated after 13 and 14 passages, respectively. Cloning and DNA sequencing of the RT region from the first resistant isolate identified a K65R mutation (AAA to AGA) in 10 of 10 clones. The role of this mutation in DXG resistance was confirmed by site-specific mutagenesis of HIV-1
LAI
. The K65R mutation also conferred greater than threefold cross-resistance to 2′,3′-dideoxycytidine, 2′,3′-dideoxyinosine, 2′,3′-dideoxy-3′-thiacytidine, 9-(2-phosphonylmethoxyethyl)adenine, 2-amino-6-chloropurine dioxolane, dioxolanyl-5-fluorocytosine, and diaminopurine dioxolane but had only marginal effects on 3′-azido-3′-deoxthymidine (AZT) susceptibility. However, when introduced into a genetic background for AZT resistance (D67N, K70R, T215Y, T219Q), the K65R mutation reversed the AZT resistance. DNA sequencing of RT clones derived from the second resistant isolate identified the L74V mutation, previously reported to cause ddI resistance. The L74V mutation also decreased the AZT resistance when the mutation was introduced into a genetic background for AZT resistance (D67N, K70R, T215Y, T219Q) but to a lesser degree than the K65R mutation did. These findings indicate that DXG and certain 2′,3′-dideoxy compounds (e.g., ddI) can select for the same resistance mutations and thus may not be optimal for use in combination. However, the combination of AZT with DXG or its orally bioavailable prodrug (−)-β-
d
-2,6-diaminopurine-dioxolane should be explored because of the suppressive effects of the K65R and L74V mutations on AZT resistance.
Synergy between Trovafloxacin and Ceftriaxone against Penicillin-Resistant Pneumococci in the Rabbit Meningitis Model and In Vitro
Authors: Cottagnoud Philippe , Acosta Fernando , Cottagnoud Marianne , Neftel Klaus , Täuber Martin G. 
Published: July 2002

ABSTRACT

The bactericidal activities of monotherapy with trovafloxacin (−0.37 ± 0.15 Δlog
10
CFU/ml · h), vancomycin (−0.32 ± 0.12 Δlog
10
CFU/ml · h), and ceftriaxone (−0.36 ± 0.19 Δlog
10
CFU/ml · h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (−0.67 ± 0.16 Δlog
10
CFU/ml · h) and was slightly superior to ceftriaxone with vancomycin (killing rate, −0.53 ± 0.22 Δlog
10
CFU/ml · h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.
Kinetic Study of the Inflammatory Response in
Streptococcus pneumoniae
Experimental Pneumonia Treated with the Ketolide HMR 3004
Authors: Duong Michel , Simard Marie , Bergeron Yves , Bergeron Michel G. 
Published: July 2002

ABSTRACT

Patients still die from
Streptococcus pneumoniae
pneumonia after initiation of antibiotic therapy, when tissues are sterile and the pneumonia is clearing. There is growing evidence that overwhelming inflammation resulting from toxin release contributes to tissue injury, shock, and death. Monitoring host response may help us understand the consequences of antibiotic therapy for the inflammatory processes that occur in bacterial pneumonia. HMR 3004 is a ketolide that displays excellent in vitro activity against
S. pneumoniae
. In the present experiment, we investigated the chronology of inflammatory events that occur during pneumococcal pneumonia in mice treated with HMR 3004. Infection of mice with 10
7
CFU of living
S. pneumoniae
resulted in 100% mortality within 5 days. HMR 3004 given at 12.5 mg/kg of body weight/dose twice daily from 48 h postinfection achieved complete bacterial clearance from lungs and blood within 36 h and ensured survival of mice. Recruitment of neutrophils and monocytes from blood to lungs was significantly reduced, and nitric oxide release was totally prevented. Interleukin-6 secretion in lungs and blood became rapidly undetectable after initiation of therapy. Histological examination of lung tissue showed protection of interstitium against edema. By controlling bacterial invasion, HMR 3004 led to rapid and profound modifications of the host response in lungs, which may protect mice from deleterious inflammatory reactions.
Use of a Recombinant Strain of
Mycobacterium avium
Expressing β-Galactosidase To Evaluate the Activities of Antimycobacterial Agents inside Macrophages
Authors: Maisetta Giuseppantonio , Batoni Giovanna , Pardini Manuela , Boschi Antonella , Bottai Daria , Esin Semih , Campa Mario , Senesi Sonia 
Published: July 2002

ABSTRACT

A reliable and low-cost method that enables rapid screening of the activity exerted by new antimicrobial agents on intracellularly growing
Mycobacterium avium
has been developed. To this aim, a recombinant (
lacZ
) strain of
M. avium
expressing the
Escherichia coli
β-galactosidase gene was used to evaluate, in murine macrophages, the susceptibility of
M. avium
to common antimycobacterial agents. β-Galactosidase levels, measured in the presence of each of the antibiotics tested, were closely correlated with the number of CFU recovered from the
M. avium lacZ
strain-infected macrophages.
Correlation between In Vitro and In Vivo Activities of GM 237354, a New Sordarin Derivative, against
Candida albicans
in an In Vitro Pharmacokinetic-Pharmacodynamic Model and Influence of Protein Binding
Authors: Aviles P. , Falcoz C. , Guillén M. J. , San Roman R. , Gómez De Las Heras F. , Gargallo-Viola D. 
Published: July 2002

ABSTRACT

The antifungal effect of GM 237354, a sordarin derivative, was studied in an in vitro pharmacokinetic (PK)-pharmacodynamic dynamic system (bioreactor) which reproduces PK profiles observed in a previously described model of drug efficacy against murine systemic candidiasis. Immunocompetent mice infected intravenously with 10
5
CFU of
Candida albicans
were treated with GM 237354 at 2.5, 10, and 40 mg/kg of body weight every 8 h subcutaneously for 7 days. Free concentrations in serum were calculated by multiplying total concentrations measured in vivo by 0.05, the free fraction determined in vitro by equilibrium dialysis. In the bioreactor the inoculum was ≈10
6
CFU/ml; and a one-compartment PK model was used to reproduce the PK profiles of free and total GM 237354 in serum obtained in mice, and clearance of
C. albicans
was measured over 48 h. A good correlation was observed when the in vivo fungal kidney burden and the area under the survival time curve were compared with the in vitro broth “burden,” although only when free in vivo levels in serum were reproduced in vitro. GM 237354 displayed a 3-log decrease effect both in vivo and in vitro. The very few reports available on in vitro-in vivo correlations have been obtained with antibiotics. The good in vitro-in vivo correlation obtained with an antifungal agent shows that the in vitro dynamic system could constitute a powerful investigational tool prior to assessment of the efficacy of an anti-infective agent in animals and humans.
Antimicrobial Susceptibilities of Clinical
Desulfovibrio
Isolates
Authors: Lozniewski A. , Labia R. , Haristoy X. , Mory F. 
Published: July 2002

ABSTRACT

The antimicrobial susceptibilities of 16 clinical isolates of
Desulfovibrio
spp. were determined. All or most isolates were susceptible to imipenem (MIC
90
[MIC at which 90% of the isolates tested were inhibited], 0.5 μg/ml), metronidazole (MIC
90
, 0.25 μg/ml), clindamycin (MIC
90
, 4 μg/ml), and chloramphenicol (MIC
90
, 16 μg/ml) but were resistant or intermediate to penicillin G (MIC
90
, 64 μg/ml), piperacillin (MIC
90
, 256 μg/ml), piperacillin-tazobactam (MIC
90
, 256 μg/ml), cefoxitin (MIC
90
, >256 μg/ml), and cefotetan (MIC
90
, 64 μg/ml). Among isolates with decreased susceptibility to β-lactams (
n
= 15), only six were β-lactamase positive and susceptible to amoxicillin-clavulanate and ticarcillin-clavulanate.
Efficacies of Clarithromycin Regimens against
Mycobacterium xenopi
in Mice
Authors: Lounis Nacer , Truffot-Pernot Chantal , Bentoucha Abdelhalim , Robert Jerome , Ji Baohong , Grosset Jacques 
Published: July 2002

ABSTRACT

Mice were infected intravenously with 3.5 × 10
7
CFU of
Mycobacterium xenopi
and treated with various clarithromycin-containing regimens or left untreated for 4 weeks. All nine of the clarithromycin-containing regimens reduced the CFU counts to the levels below the pretreatment values, indicating that these regimens had a bactericidal effect on
M. xenopi
in mice. The rifampin-isoniazid-ethambutol regimen was significantly less bactericidal than clarithromycin alone or clarithromycin-containing combined regimens.
Staphylococcus aureus
Mutants Selected by BMS-284756
Authors: Discotto L. F. , Lawrence L. E. , Denbleyker K. L. , Barrett J. F. 
Published: July 2002

ABSTRACT

BMS-284756, a novel des-fluoro(6)-quinolone, was used to select for in vitro mutants of
Staphylococcus aureus
ISP794. Step mutants were obtained, and the quinolone resistance-determining regions of four target genes,
gyrA, gyrB, grlA
, and
grlB
, were sequenced. The data suggest that DNA gyrase is the primary target for BMS-284756 in
S. aureus
.
Postantibiotic Effects of ABT-773 and Amoxicillin-Clavulanate against
Streptococcus pneumoniae
and
Haemophilus influenzae
Authors: Neuhauser Melinda M. , Prause Jennifer L. , Danziger Larry H. , Pendland Susan L. 
Published: July 2002

ABSTRACT

This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates of
Streptococcus pneumoniae
and
Haemophilus influenzae
. The PAEs of ABT-773 and amoxicillin-clavulanate ranged from 2.3 to 6.0 h and 0 to 2.2 h against
S. pneumoniae
and from 2.7 to 9.1 h and 0 to 0.8 h against
H. influenzae
, respectively.
Pharmacokinetic Study of Human Immunodeficiency Virus Protease Inhibitors Used in Combination with Amprenavir
Authors: Sadler Brian M. , Gillotin Catherine , Lou Yu , Eron Joseph J. , Lang William , Haubrich Richard , Stein Daniel S. 
Published: July 2002

ABSTRACT

In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUC
ss
] and 37% for peak plasma concentration at steady state [
C
max,ss
]) and increased by indinavir (33% for AUC
ss
). Nelfinavir significantly increased amprenavir minimum drug concentration at steady state (by 189%) but did not affect amprenavir AUC
ss
or
C
max,ss
. Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in amprenavir steady-state pharmacokinetic parameters, relative to those for amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.
Differential Selection of Multidrug Efflux Mutants by Trovafloxacin and Ciprofloxacin in an Experimental Model of
Pseudomonas aeruginosa
Acute Pneumonia in Rats
Authors: Join-Lambert O. F. , Michéa-Hamzehpour M. , Köhler T. , Chau F. , Faurisson F. , Dautrey S. , Vissuzaine C. , Carbon C. , Pechère J.-C. 
Published: July 2002

ABSTRACT

The ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo was studied in a model of acute
Pseudomonas aeruginosa
pneumonia in rats. Twelve hours after intratracheal inoculation of 10
6
CFU of
P. aeruginosa
strain PAO1 enmeshed in agar beads, two groups of 12 rats were treated by three intraperitoneal injections of each antibiotic given every 5 h. Dosing regimens were chosen to obtain a comparable area under the concentration-time curve from 0 to infinity/MIC ratio of 27.9 min for trovafloxacin (75 mg/kg of body weight) and of 32.6 min for ciprofloxacin (12.5 mg/kg). Twelve rats were left untreated and served as controls. Rats were sacrificed 12 h after the last injection (34 h after infection) for lung bacteriological studies. Selection of resistant bacteria was determined by plating lung homogenates on Trypticase soy agar plates containing antibiotic. In untreated animals, the frequency of resistant colonies was 10-fold higher than in agar beads. Compared to controls, both treatment regimens resulted in a 2-log reduction of lung bacterial load. The frequency of resistant colonies was 10-fold less with trovafloxacin than with ciprofloxacin at twice the MIC (7.4 × 10
−5
versus 8.4 × 10
−4
, respectively) (
P
< 0.05) and at four times the MIC (6.2 × 10
−4
versus 5.0 × 10
−5
, respectively) (
P
< 0.05). A multidrug resistance phenotype typical of efflux mutants was observed in all 41 randomly tested colonies obtained from treated and untreated rats. In agreement with in vitro results, trovafloxacin and ciprofloxacin preferentially selected MexCD-OprJ and MexEF-OprN overproducers, respectively. These results demonstrate the differential ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo and highlight the rapid emergence of those mutants, even without treatment.
Nucleotide Sequence and Characterization of a Novel Cefotaxime-Hydrolyzing β-Lactamase (CTX-M-10) Isolated in Spain
Authors: Oliver Antonio , Pérez-Dı́az José Claudio , Coque Teresa M. , Baquero Fernando , Cantón Rafael 
Published: July 2002

ABSTRACT

A cefotaxime-resistant, ceftazidime-susceptible
Escherichia coli
isolate was obtained from a patient with sepsis in 1997, from which a β-lactamase with a pI of 8.1 was cloned. Cephaloridine and cefotaxime relative hydrolysis rates were 167 and 81, respectively (penicillin G rate = 100), whereas ceftazidime hydrolysis was not detected. The nucleotide sequence revealed a
bla
gene related to that coding for CTX-M-3. Despite 21 nucleotide substitutions, only 2 determined amino acid changes (Ala27Val and Arg38Gln). The amino acid sequence identity between this enzyme, designated CTX-M-10, and the chromosomal β-lactamase of
Kluyvera ascorbata
was 81%.
Macrolide Resistance in
Peptostreptococcus
spp. Mediated by
ermTR
: Possible Source of Macrolide-Lincosamide-Streptogramin B Resistance in
Streptococcus pyogenes
Authors: Reig Milagro , Galan Juan-Carlos , Baquero Fernando , Perez-Diaz Jose Claudio 
Published: July 2002

ABSTRACT

Eighty percent (21 of 26) of macrolide-resistant
Peptostreptococcus
strains studied harbored the
ermTR
gene. This methyltransferase gene is also the most frequently found gene among macrolide-lincosamide-streptogramin B-resistant
Streptococcus pyogenes
strains. Transfer of the
ermTR
gene from
Peptostreptococcus magnus
to macrolide-susceptible
S. pyogenes
strains indicates that this resistance determinant may circulate among gram-positive aerobic and anaerobic species of the oropharyngeal bacterial flora.
Quinolone Resistance in Staphylococci: Activities of New Nonfluorinated Quinolones against Molecular Targets in Whole Cells and Clinical Isolates
Authors: Roychoudhury Siddhartha , Catrenich Carl E. , McIntosh Eric J. , McKeever Helana D. , Makin Kelly M. , Koenigs Paula M. , Ledoussal Benoit 
Published: July 2002

ABSTRACT

The activity of three new, 8-methoxy-nonfluorinated quinolones (NFQs) against multiple-drug-resistant staphylococci was investigated. First, using
Staphylococcus aureus
strains containing point mutations in the serine 84–80 hot spots of the target genes (
gyrA
and
grlA
), cell growth inhibition potencies of the NFQs as a result of DNA gyrase and topoisomerase IV inhibition were estimated and compared with those of known fluoroquinolones. The NFQs and clinafloxacin showed higher affinities toward both the targets than ciprofloxacin, trovafloxacin and gatifloxacin. Furthermore, the ratio of the calculated affinity parameter for DNA gyrase to that for topoisomerase IV was lower in the case of the NFQs, clinafloxacin, and gatifloxacin than in the case of ciprofloxacin and trovafloxacin. These results suggest that the former group of quinolones is better able to exploit both the targets. Next, using clinical isolates of methicillin-resistant
S. aureus
(MRSA;
n
= 34) and coagulase-negative staphylococci (CoNS;
n
= 24), the NFQs and clinafloxacin were shown to be more potent (MIC at which 90% of the isolates are inhibited [MIC
90
] = 2 μg/ml for MRSA and 0.5 μg/ml for CoNS) than ciprofloxacin, trovafloxacin, and gatifloxacin (MIC
90
= 16 to >64 μg/ml for MRSA and 4 to >32 μg/ml for CoNS). Bactericidal kinetics experiments, using two MRSA isolates, showed that exposure to the NFQs at four times the MIC reduced the bacterial counts (measured in CFU per milliliter) by ≥3 log units in 2 to 4 h. Overall, the NFQs and clinafloxacin were less susceptible than the other quinolones to existing mechanisms of quinolone resistance in staphylococci.
In Vitro and in Vivo Combinations of Cefotaxime and Minocycline against
Aeromonas hydrophila
Authors: Ko Wen-Chien , Lee Hsin-Chun , Chuang Yin-Ching , Ten Shih-Hua , Su Chia-Yang , Wu Jiunn-Jong 
Published: July 2002

ABSTRACT

The activities of cefotaxime and minocycline against
Aeromonas hydrophila
were investigated. Cefotaxime (4 times the MIC) plus minocycline (0.75 times the MIC) elicited an inhibitory effect for 48 h in a time-kill study, and more infected mice treated with both drugs survived (91%) than survived after treatment with cefotaxime (9%) or minocycline (44%) alone, suggesting that cefotaxime and minocycline act synergistically against
A. hydrophila
.
Pharmacodynamic Assessment of Gatifloxacin against
Streptococcus pneumoniae
Authors: Mattoes Holly M. , Banevicius Maryanne , Li Dadong , Turley Christina , Xuan Dawei , Nightingale Charles H. , Nicolau David P. 
Published: July 2002

ABSTRACT

The pharmacodynamic parameters of peak serum drug concentration/MIC (peak/MIC) ratio and the area under the curve (AUC)/MIC ratio have been used to characterize in vivo drug exposure and its relationship to bacterial killing for the fluoroquinolones. Our study objectives were to describe the pharmacodynamic relationship between gatifloxacin exposure and outcome as assessed by bacterial density and survival in an immunocompromised murine thigh model of pneumococcal infection and to assess the relationship between drug exposure and these outcomes in an immunocompetent host. ICR mice were rendered neutropenic, and thigh infection was induced by intramuscular administration of 0.1 ml of 10
5
to 10
7
CFU of
Streptococcus pneumoniae
/ml. Mice received 1 to 5 mg of uranyl nitrate/kg of body weight at day −3 and were randomized to receive 10 to 80 mg of gatifloxacin/kg every 6 to 24 h orally, starting at 2 h postinoculation. Bacterial density studies were completed 24 h after initiation of therapy, and survival was assessed after 4 days of treatment. MICs for clinical isolates (
n
= 8) ranged from 0.25 to 1.0 μg/ml. Correlations were assessed between the change in bacterial density, as well as survival, and the AUC/MIC ratio, peak/MIC ratio, and the duration of time that serum drug concentration remained above the MIC. The best predictor of bacterial response was the AUC/MIC ratio for both outcome measures. There was greater efficacy, as measured by a decrease in log change in CFU as well as by survival data, in the immunocompetent mice compared to the immunocompromised mice. These data demonstrate (i) the appropriateness of the AUC/MIC ratio as a dynamic predictor of response to pneumococcal infection for the fluoroquinolones, (ii) that gatifloxacin AUC/MIC ratios of 30 to 40 appear to optimize bactericidal activity and survival in this model, and (iii) that immunocompetency of the host plays a role in efficacy.