bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Pharmacokinetics of Ciprofloxacin, Gatifloxacin, Grepafloxacin, Levofloxacin, Trovafloxacin, and Moxifloxacin after Single Oral Administration in Healthy Volunteers
Authors: Lubasch Annette , Keller Ivonne , Borner Klaus , Koeppe Peter , Lode Hartmut 
Published: July 2002

ABSTRACT

In an open, randomized, six-period crossover study, the pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin were compared after a single oral dose in 12 healthy volunteers (6 men and 6 women). The volunteers received 250 mg of ciprofloxacin, 400 mg of gatifloxacin, 600 mg of grepafloxacin, 500 mg of levofloxacin, 400 mg of moxifloxacin, and 200 mg of trovafloxacin. The concentrations of the six fluoroquinolones in serum and urine were measured by a validated high-performance liquid chromatography method. Blood and urine samples were collected before and at different time points up to 48 h after medication. Levofloxacin had the highest peak concentration (
C
max
, in micrograms per milliliter) (6.21 ± 1.34), followed by moxifloxacin (4.34 ± 1.61) and gatifloxacin (3.42 ± 0.74). Elimination half-lives ranged from 12.12 ± 3.93 h (grepafloxacin) to 5.37 ± 0.82 h (ciprofloxacin). The total areas under the curve (AUC
tot
, in microgram-hours per milliliter) for levofloxacin (44.8 ± 4.4), moxifloxacin (39.3 ± 5.35), and gatifloxacin (30 ± 3.8) were significantly higher than that for ciprofloxacin (5.75 ± 1.25). Calculated from a normalized dose of 200 mg, the highest
C
max
s (in micrograms per milliliter) were observed for levofloxacin (2.48 ± 0.53), followed by moxifloxacin (2.17 ± 0.81) and trovafloxacin (2.09 ± 0.58). The highest AUC
tot
(in microgram-hours per milliliter) for a 200-mg dose were observed for moxifloxacin (19.7 ± 2.67) and trovafloxacin (19.5 ± 3.1); the lowest was observed for ciprofloxacin (4.6 ± 1.0). No serious adverse event was observed during the study period. The five recently developed fluoroquinolones (gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin) showed greater bioavailability, longer half-lives, and higher
C
max
s than ciprofloxacin.
Anti-
Candida
Activity of a New Platinum Derivative
Authors: Watanabe T. , Takano M. , Ogasawara A. , Mikami T. , Kobayashi T. , Watabe M. , Matsumoto T. 
Published: July 2002

ABSTRACT

A new platinum derivative of the form H[Pt(IV)(Hdigly)Cl
2
(OH)
2
] (Hdiglyglycylglycine) damaged the
Candida albicans
cell membrane and inhibited the growth of the cells. The cytotoxic activity of H[Pt(IV)(Hdigly)Cl
2
(OH)
2
] on mammalian cells was 10-fold lower than that of
cis
-diammine-dichloroplatinum (cisplatin). Substitution of platinum for peptides is effective for enhancement of antifungal activity and reduction of the toxicity to mammalian cells.
Genetic Diversity of the
tet
(M) Gene in Tetracycline-Resistant Clonal Lineages of
Streptococcus pneumoniae
Authors: Doherty Neil , Trzcinski Krzysztof , Pickerill Paul , Zawadzki Piotr , Dowson Christopher G. 
Published: July 2002

ABSTRACT

The aim of the present study was to examine the stability and evolution of
tet
(M)-mediated resistance to tetracyclines among members of different clonal lineages of
Streptococcus pneumoniae
. Thirty-two tetracycline-resistant isolates representing three national (Spanish serotype 14, Spanish serotype 15, and Polish serotype 23F) and one international (Spanish serotype 23F) multidrug-resistant epidemic clones were all found to be
tet
(M) positive and
tet
(O),
tet
(K), and
tet
(L) negative. These isolates all carried the integrase gene,
int
, which is associated with the Tn
1545
-Tn
916
family of conjugative transposons. High-resolution restriction analysis of
tet
(M) products identified six alleles,
tet
(M)1 to
tet
(M)6:
tet
(M)1 to
tet
(M)3 and
tet
(M)5 in isolates of the Spanish serotype 14 clone,
tet
(M)4 in both the Spanish serotype 15 and 23F clones, and
tet
(M)6, the most divergent allele, in the Polish 23F clone. This indicates that
tet
(M) variation can occur at the inter- and intraclone levels in pneumococci. Two alleles of
int
were identified, with
int1
being found in all isolates apart from members of the international Spanish 23F clone, which carried
int2
. Susceptibility to tetracycline, doxycycline, and minocycline was evaluated for all isolates with or without preincubation in the presence of subinhibitory concentrations of tetracyclines. Resistance to tetracyclines was found to be inducible in isolates of all clones; however, the strongest induction was observed in the Spanish serotype 15 and 23F clones carrying
tet
(M)4. Tetracycline was found to be the strongest inducer of resistance, and minocycline was found to be the weakest inducer of resistance.
Genetic Analysis of Azole Resistance in the Darlington Strain of
Candida albicans
Authors: Kakeya Hiroshi , Miyazaki Yoshitsugu , Miyazaki Haruko , Nyswaner Katherine , Grimberg Brian , Bennett John E. 
Published: July 2002

ABSTRACT

High-level azole resistance in the Darlington strain of
Candida albicans
was investigated by gene replacement in
C. albicans
and expression in
Saccharomyces cerevisiae
. We sequenced the
ERG11
gene, which encodes the sterol C
14
α-demethylase, from our copy of the Darlington strain. Both alleles contained the histidine for tyrosine substitution at position 132 (Y132H) reported in Darlington by others, but we also found a threonine-for-isoleucine substitution (I471T) not previously reported in the
C. albicans ERG11
. The encoded I471T change in amino acids conferred azole resistance when overexpressed alone and increased azole resistance when added to the Y132H amino acid sequence in an
S. cerevisiae
expression system. Replacement of one copy of
ERG11
in an azole-susceptible strain of
C. albicans
with a single copy of the Darlington
ERG11
resulted in expression of the integrated copy and a modest increase in azole resistance. The profound azole resistance of the Darlington strain is the result of multiple mutations.
Flow Cytometric Detection of
Leishmania
Parasites in Human Monocyte-Derived Macrophages: Application to Antileishmanial-Drug Testing
Authors: Di Giorgio C. , Ridoux O. , Delmas F. , Azas N. , Gasquet M. , Timon-David P. 
Published: July 2002

ABSTRACT

A flow cytometric technique was developed for detection of amastigotes of the protozoan
Leishmania infantum
in human nonadherent monocyte-derived macrophages. The cells were fixed and permeabilized with paraformaldehyde-ethanol, and intracellular amastigotes were labeled with
Leishmania
lipophosphoglycan-specific monoclonal antibody. Results showed that flow cytometry provided accurate quantification of the infection rates in human macrophages compared to the rates obtained by the conventional microscopic technique, with the advantage that a large number of cells could be analyzed rapidly. The results demonstrated, moreover, that labeling of intracellular amastigotes could reliably be used to evaluate the antileishmanial activities of conventional drugs such as meglumine antimoniate, amphotericin B, pentamidine, and allopurinol. They also established that various
Leishmania
species (
L. mexicana
,
L. donovani
) could be detected by this technique in other host-cell models such as mouse peritoneal macrophages and suggested that the flow cytometric method could be a valid alternative to the conventional method.
Use of Cotton Rats to Evaluate the Efficacy of Antivirals in Treatment of Measles Virus Infections
Authors: Wyde Philip R. , Moore-Poveda Donna K. , De Clercq Erik , Neyts Johan , Matsuda Akira , Minakawa Noriaki , Guzman Efrain , Gilbert Brian E. 
Published: July 2002

ABSTRACTNo practical animal models for the testing of chemotherapeutic or biologic agents identified in cell culture assays as being active against measles virus (MV) are currently available. Cotton rats may serve this purpose. To evaluate this possibility, 5-ethynyl-1-β-d-ribofuranosylimidazole-4-carboxamide (EICAR) and poly(acrylamidomethyl propanesulfonate) (PAMPS), two compounds that have been reported to inhibit MV in vitro, and ribavirin, an established antiviral drug with MV-inhibitory activity, were evaluated for their antiviral activities against MV and respiratory syncytial virus (RSV) in tissue culture and in hispid cotton rats. A single administration of PAMPS markedly inhibited pulmonary RSV or MV replication (>3 log10reduction in pulmonary titer compared to that for controls), but only if this compound was administered intranasally at about the time of virus inoculation. Both EICAR and ribavirin exhibited therapeutic activity against RSV and MV in cotton rats when they were administered parenterally. However, both of these compounds were less effective against MV. On the basis of the pulmonary virus titers on day 4 after virus inoculation, the minimal efficacious dose of EICAR against MV (120 mg/kg of body weight/day when delivered intraperitoneally twice daily) appeared to be three times lower against this virus than that of ribavirin delivered at a similar dose (i.e., 360 mg/kg/day). These findings correlated with those obtained in vitro. The data obtained suggest that cotton rats may indeed be useful for the initial evaluation of the activities of antiviral agents against MV.
Cerebrospinal Fluid Penetration and Pharmacokinetics of Vancomycin Administered by Continuous Infusion to Mechanically Ventilated Patients in an Intensive Care Unit
Authors: Albanèse Jacques , Léone Marc , Bruguerolle Bernard , Ayem Marie-Laure , Lacarelle Bruno , Martin Claude 
Published: July 2002

ABSTRACT

Cerebrospinal fluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after continuous infusion (50 to 60 mg/kg of body weight/day after a loading dose of 15 mg/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit. Seven patients were treated for a sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic disease with intracranial hypertension, were treated for various infections. Vancomycin CSF penetration was significantly higher (
P
< 0.05) in the meningitis group (serum/CSF ratio, 48%) than in the other group (serum/CSF ratio, 18%). Vancomycin pharmacokinetic parameters did not differ from those obtained with conventional dosing. No adverse effect was observed, in particular with regard to renal function.
Furazolidone- and Nitrofurantoin-Resistant
Helicobacter pylori
: Prevalence and Role of Genes Involved in Metronidazole Resistance
Authors: Kwon Dong H. , Lee Miae , Kim J. J. , Kim J. G. , El-Zaatari F. A. K. , Osato M. S. , Graham D. Y. 
Published: July 2002

ABSTRACT

The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among
Helicobacter pylori
strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant.
rdxA
,
frxA
, and
fdxB
knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating
H. pylori
infection.
Effective Combination Therapy for Invasive Pneumococcal Pneumonia with Ampicillin and Intravenous Immunoglobulins in a Mouse Model
Authors: De Hennezel Laetitia , Ramisse Françoise , Binder Patrice , Marchal Gilles , Alonso Jean-Michel 
Published: July 2002

ABSTRACTIntranasal immunotherapy forStreptococcus pneumoniaeinvasive pneumonia with polyvalent immunoglobulins (IVIG) was effective in mice against pneumonia but failed to prevent bacteremia. The combination of subcurative doses of IVIG and of ampicillin was fully protective. Such an approach, successfully applied in the preantibiotic era, offers new perspectives for modern therapies.
Biochemical Characterization of the FEZ-1 Metallo-β-Lactamase of
Legionella gormanii
ATCC 33297
T
Produced in
Escherichia coli
Authors: Mercuri Paola Sandra , Bouillenne Fabrice , Boschi Letizia , Lamotte-Brasseur Josette , Amicosante Gianfranco , Devreese Bart , van Beeumen Jozef , Frère Jean-Marie , Rossolini Gian Maria , Galleni Moreno 
Published: July 2002

ABSTRACT

The
bla
FEZ-1
gene coding for the metallo-β-lactamase of
Legionella (Fluoribacter) gormanii
ATCC 33297
T
was overexpressed via a T7 expression system in
Escherichia coli
BL21(DE3)(pLysS). The product was purified to homogeneity in two steps with a yield of 53%. The FEZ-1 metallo-β-lactamase exhibited a broad-spectrum activity profile, with a preference for cephalosporins such as cephalothin, cefuroxime, and cefotaxime. Monobactams were not hydrolyzed. The β-lactamase was inhibited by metal chelators. FEZ-1 is a monomeric enzyme with a molecular mass of 29,440 Da which possesses two zinc-binding sites. Its zinc content did not vary in the pH range of 5 to 9, but the presence of zinc ions modified the catalytic efficiency of the enzyme. A model of the FEZ-1 three-dimensional structure was built.
Molecular Basis of Rifampin and Isoniazid Resistance in
Mycobacterium bovis
Strains Isolated in Sardinia, Italy
Authors: Sechi L. A. , Zanetti S. , Sanguinetti M. , Molicotti P. , Romano L. , Leori G. , Delogu G. , Boccia S. , La Sorda M. , Fadda G. 
Published: July 2002

ABSTRACT

Fourteen of 22 (68%)
Mycobacterium bovis
strains isolated from cattle in Sardinia were found to be resistant to rifampin and isoniazid. Analysis of the
rpoB
and the
katG, oxyR-ahpC
, and
inhA
gene regions of these strains was performed in order to investigate the molecular basis of rifampin and isoniazid resistance, respectively. The most frequent mutation, encountered in 6 of 10 strains (60%), was in the
rpoB
gene; it occurred, at codon position 521 and resulted in leucine changed to proline. This suggests that codon 521 may be important for the development of rifampin resistance in
M. bovis
. Resistance to isoniazid is associated in
Mycobacterium tuberculosis
with a variety of mutations affecting one or more genes. Our results confirm the difficulty of interpreting the sequence variations observed in clinical strains of
M. bovis. M. bovis
strains isolated from the same geographic area showed similar mutations within the genes responsible for rifampin and isoniazid resistance. Our results represent the first study to elucidate the molecular genetic basis of drug resistance in
M. bovis
isolated from cattle.
Macrolide Resistance Gene
mreA
of
Streptococcus agalactiae
Encodes a Flavokinase
Authors: Clarebout Gervais , Villers Corinne , Leclercq Roland 
Published: July 2002

ABSTRACT

The
mreA
gene from
Streptococcus agalactiae
COH31 γ/δ, resistant to macrolides and clindamycin by active efflux, has recently been cloned in
Escherichia coli
, where it was reported to confer macrolide resistance (J. Clancy, F. Dib-Hajj, J. W. Petitpas, and W. Yuan, Antimicrob. Agents Chemother. 41:2719–2723, 1997). Cumulative data suggested that the
mreA
gene was located on the chromosome of
S. agalactiae
COH31 γ/δ. Analysis of the deduced amino acid sequence of
mreA
revealed significant homology with several bifunctional flavokinases/(flavin adenine dinucleotide (FAD) synthetases, which convert riboflavin to flavin mononucleotide (FMN) and FMN to FAD, respectively. High-performance liquid chromatography experiments showed that the
mreA
gene product had a monofunctional flavokinase activity, similar to that of RibR from
Bacillus subtilis
. Sequences identical to those of the
mreA
gene and of a 121-bp upstream region containing a putative promoter were detected in strains of
S. agalactiae
UCN4, UCN5, and UCN6 susceptible to macrolides.
mreA
and its allele from
S. agalactiae
UCN4 were cloned on the shuttle vector pAT28. Both constructs were introduced into
E. coli
, where they conferred a similar two- to fourfold increase in the MICs of erythromycin, spiramycin, and clindamycin. The MICs of a variety of other molecules, including crystal violet, acriflavin, sodium dodecyl sulfate, and antibiotics, such as certain cephalosporins, chloramphenicol, doxycycline, nalidixic acid, novobiocin, and rifampin, were also increased. In contrast, resistance to these compounds was not detected when the constructs were introduced into
E. faecalis
JH2–2. In conclusion, the
mreA
gene was probably resident in
S. agalactiae
and may encode a metabolic function. We could not provide any evidence that it was responsible for macrolide resistance in
S. agalactiae
COH31 γ/δ; broad-spectrum resistance conferred by the gene in
E. coli
could involve multidrug efflux pumps by a mechanism that remains to be elucidated.
Assessment of Mitochondrial Toxicity in Human Cells Treated with Tenofovir: Comparison with Other Nucleoside Reverse Transcriptase Inhibitors
Authors: Birkus Gabriel , Hitchcock Michael J. M. , Cihlar Tomas 
Published: July 2002

ABSTRACT

Drug-associated dysfunction of mitochondria is believed to play a role in the etiology of the various adverse symptoms that occur in human immunodeficiency virus (HIV)-infected patients treated with the nucleoside reverse transcriptase inhibitors (NRTIs). Tenofovir, a nucleotide analog recently approved for use in the treatment of HIV infection, was evaluated in vitro for its potential to cause mitochondrial toxicity and was compared to currently used NRTIs. Treatment with tenofovir (3 to 300 μM) for up to 3 weeks produced no significant changes in mitochondrial DNA (mtDNA) levels in human hepatoblastoma (HepG2) cells, skeletal muscle cells (SkMCs), or renal proximal tubule epithelial cells. The potencies of inhibition of mtDNA synthesis by the NRTIs tested were zalcitabine (ddC) > didanosine (ddI) > stavudine > zidovudine (ZDV) > lamivudine = abacavir = tenofovir, with comparable relative effects in the three cell types. Unlike ddC and ddI, tenofovir did not affect cellular expression of COX II and COX IV, two components of the mitochondrial cytochrome
c
oxidase complex. Lactate production was elevated by less than 20% in HepG2 cells or SkMCs following treatment with 300 μM tenofovir. In contrast, lactate synthesis increased by >200% in the presence of 300 μM ZDV. Thus, treatment of various human cell types with tenofovir at concentrations that greatly exceed those required for it both to have in vitro anti-HIV type 1 activity in peripheral blood mononuclear cells (50% effective concentration, 0.2 μM) and to achieve therapeutically relevant levels in plasma (maximum concentrations in plasma, 0.8 to 1.3 μM) is not associated with mitochondrial toxicity.
Antileishmanial Activities of Several Classes of Aromatic Dications
Authors: Brendle James J. , Outlaw Abram , Kumar Arvind , Boykin David W. , Patrick Donald A. , Tidwell Richard R. , Werbovetz Karl A. 
Published: July 2002

ABSTRACT

Aromatic dicationic molecules possess impressive activity against a broad spectrum of microbial pathogens, including
Pneumocystis carinii
,
Cryptosporidium parvum
, and
Candida albicans
. In this work, 58 aromatic cations were examined for inhibitory activity against axenic amastigote-like
Leishmania donovani
parasites. In general, the most potent of the compounds were substituted diphenyl furan and thiophene dications. 2,5-Bis-(4-amidinophenyl)thiophene was the most active compound. This agent displayed a 50% inhibitory concentration (IC
50
) of 0.42 ± 0.08 μM against
L. donovani
and an in vitro antileishmanial potency 6.2-fold greater than that of the clinical antileishmanial dication pentamidine and was 155-fold more toxic to the parasites than to a mouse macrophage cell line. 2,4-Bis-(4-amidinopheny)furan was twice as active as pentamidine (IC
50
, 1.30 ± 0.21 μM), while 2,5-bis-(4-amidinopheny)furan and pentamidine were essentially equipotent in our in vitro antileishmanial assay. Carbazoles, dibenzofurans, dibenzothiophenes, and benzimidazoles containing amidine or substituted amidine groups were generally less active than the diphenyl furans and thiophenes. In all cases, aromatic dications possessing strong antileishmanial activity were severalfold more toxic to the parasites than to a cultured mouse macrophage cell line. These structure-activity relationships demonstrate the potent antileishmanial activity of several aromatic dications and provide valuable information for the future design and synthesis of more potent antiparasitic agents.
Extent of Cross-Resistance between Agents Used To Treat Human Immunodeficiency Virus Type 1 Infection in Clinically Derived Isolates
Authors: Harrigan P. Richard , Larder Brendan A. 
Published: July 2002

ABSTRACT
The phenomenon of cross-resistance to antiretroviral agents used to treat human immunodeficiency virus type 1 infection is well known but so far has been only qualitatively described. Here, we quantitate the degree of cross-resistance among all commonly prescribed antiretroviral agents in almost 5,000 clinically derived recombinant isolates collected in the United States since January 2000.
Effects of Chemical and Physical Agents on Viability and Infectivity of
Encephalitozoon intestinalis
Determined by Cell Culture and Flow Cytometry
Authors: Santillana-Hayat Maud , Sarfati Claudine , Fournier Sandra , Chau Françoise , Porcher Raphaël , Molina Jean-Michel , Derouin Francis 
Published: July 2002

ABSTRACT

We combined tissue culture and flow cytometry to assess the activities of various temperatures, chemicals, and disinfectants on the viability and infectivity of spores of
Encephalitozoon intestinalis
. Surfanios and benzalkonium chloride, disinfectants currently used in the hospital, were remarkably efficient in destroying spore viability and infectivity.
Rhizosphere Competitiveness of Trichloroethylene-Degrading, Poplar-Colonizing Recombinant Bacteria
Authors: Shim Hojae , Chauhan Sadhana , Ryoo Doohyun , Bowers Kally , Thomas Stuart M. , Canada Keith A. , Burken Joel G. , Wood Thomas K. 
Published: July 2002

ABSTRACT

Indigenous bacteria from poplar tree (
Populus canadensis
var.
eugenei
‘Imperial Carolina’) and southern California shrub rhizospheres, as well as two tree-colonizing
Rhizobium
strains (ATCC 10320 and ATCC 35645), were engineered to express constitutively and stably toluene
o
-monooxygenase (TOM) from
Burkholderia cepacia
G4 by integrating the
tom
locus into the chromosome. The poplar and
Rhizobium
recombinant bacteria degraded trichloroethylene at a rate of 0.8 to 2.1 nmol/min/mg of protein and were competitive against the unengineered hosts in wheat and barley rhizospheres for 1 month (colonization occurred at a level of 1.0 × 10
5
to 23 × 10
5
CFU/cm of root). In addition, six of these recombinants colonized poplar roots stably and competitively with populations as large as 79% ± 12% of all rhizosphere bacteria after 28 days (0.2 × 10
5
to 31 × 10
5
CFU/cm of root). Furthermore, five of the most competitive poplar recombinants (e.g., Pb3-1 and Pb5-1, which were identified as
Pseudomonas
sp. strain PsK recombinants) retained the ability to express TOM for 29 days as 100% ± 0% of the recombinants detected in the poplar rhizosphere expressed TOM constitutively.
Characterization of
Bacillus
Species Used for Oral Bacteriotherapy and Bacterioprophylaxis of Gastrointestinal Disorders
Authors: Hoa Ngo Thi , Baccigalupi Loredana , Huxham Ashley , Smertenko Andrei , Van Pham Hung , Ammendola Sergio , Ricca Ezio , Cutting Simon M. 
Published: July 2002

ABSTRACT

Bacillus subtilis
spores are being used for oral bacteriotherapy and bacterioprophylaxis of gastrointestinal disorders in both humans and animals. Since
B. subtilis
is an aerobic saprophyte, how spores may benefit the gut microbiota is an intriguing question, since other probiotics such as
Lactobacillus
spp. which colonize the gut are anerobes. As a first step in understanding the potential effects of ingesting spores, we have characterized five commercial products. An extensive biochemical, physiological, and phylogenetic analysis has revealed that four of these products are mislabeled. Moreover, four of these products showed high levels of antibiotic resistance.