bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerance and Pharmacokinetic Interactions of Rifabutin and Clarithromycin in Human Immunodeficiency Virus-Infected Volunteers
Authors: Hafner Richard , Bethel James , Power Maureen , Landry Bernard , Banach Mary , Mole Larry , Standiford Harold C. , Follansbee Stephen , Kumar Princy , Raasch Ralph , Cohn David , Mushatt David , Drusano George 
Published: October 2018

ABSTRACT

This study evaluated the tolerance and potential pharmacokinetic interactions between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in clinically stable human immunodeficiency virus-infected volunteers with CD4 counts of <200 cells/mm
3
. Thirty-four subjects were randomized equally to either regimen A or regimen B. On days 1 to 14, subjects assigned to regimen A received clarithromycin and subjects assigned to regimen B received rifabutin, and then both groups received both drugs on days 15 to 42. Of the 14 regimen A and the 15 regimen B subjects who started combination therapy, 1 subject in each group prematurely discontinued therapy due to toxicity, but 19 of 29 subjects reported nausea, vomiting, and/or diarrhea. Pharmacokinetic analysis included data for 11 regimen A and 14 regimen B subjects. Steady-state pharmacokinetic parameters for single-agent therapy (day 14) and combination therapy (day 42) were compared. Regimen A resulted in a mean decrease of 44% (
P
= 0.003) in the clarithromycin area under the plasma concentration-time curve (AUC), while there was a mean increase of 57% (
P
= 0.004) in the AUC of the clarithromycin metabolite 14-OH-clarithromycin. Regimen B resulted in a mean increase of 99% (
P
= 0.001) in the rifabutin AUC and a mean increase of 375% (
P
< 0.001) in the AUC of the rifabutin metabolite 25-
O
-desacetyl-rifabutin. The usefulness of this combination for prophylaxis of
Mycobacterium avium
infections is limited by frequent gastrointestinal adverse events. Coadministration of clarithromycin and rifabutin results in significant bidirectional pharmacokinetic interactions. The resulting increase in rifabutin levels may explain the increased frequency of uveitis observed with concomitant use of these drugs.
Short- and Long-Term Efficacy of Hexadecylphosphocholine against EstablishedLeishmania infantumInfection in BALB/c Mice
Authors: Le Fichoux Yves , Rousseau Déborah , Ferrua Bernard , Ruette Sandrine , Lelièvre Alain , Grousson Dominique , Kubar Joanna 
Published: October 2018

ABSTRACTIn the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if untreated. In immunosuppressed patients, VL is an opportunistic infection for which there is no effective treatment for relapses. Here we report on the long-term activity of orally administered hexadecylphosphocholine (HDPC) against establishedLeishmania infantuminfection in BALB/c mice. HDPC is a synthetic phospholipid with antiproliferative properties that has been extensively studied for its cancerostatic activity. Its short-term leishmanicidal effects in mice recently infected with viscerotropicLeishmaniaspecies have been previously reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body weight/day) led to amastigote suppression in the liver and the spleen of 94 and 78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the liver and spleen, respectively), in mice infected 6 weeks before treatment and examined 3 days after the end of treatment. These results demonstrate the short-term efficacy of HDPC against an establishedLeishmaniainfection. Next, the long-term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52 days after the end of the treatment. In the treated mice, the increase of the splenic load was significantly slower than that in the untreated mice, demonstrating that the HDPC-exerted inhibition ofLeishmaniagrowth persisted for at least 7 to 8 weeks. Orally administered HDPC—the safe doses and side effects of which are at least partially known—appears to be a promising candidate for the treatment of VL.
The Antibiotic Micrococcin Is a Potent Inhibitor of Growth and Protein Synthesis in the Malaria Parasite
Authors: Rogers M. John , Cundliffe Eric , McCutchan Thomas F. 
Published: October 2018

ABSTRACT

The antibiotic micrococcin is a potent growth inhibitor of the human malaria parasite
Plasmodium falciparum
, with a 50% inhibitory concentration of 35 nM. This is comparable to or less than the corresponding levels of commonly used antimalarial drugs. Micrococcin, like thiostrepton, putatively targets protein synthesis in the plastid-like organelle of the parasite.
Analysis of Diversity of Mutations in the
mecI
Gene and
mecA
Promoter/Operator Region of Methicillin-Resistant
Staphylococcus aureus
and
Staphylococcus epidermidis
Authors: Kobayashi Nobumichi , Taniguchi Koki , Urasawa Shozo 
Published: October 2018

ABSTRACT

Genomic diversity of mutation in the
mecI
gene or
mecA
promoter/operator region was analyzed for clinical isolates of methicillin-resistant
Staphylococcus aureus
(MRSA) and
Staphylococcus epidermidis
(MRSE). In most MRSA strains, a single base substitution was detected in either the
mecI
(three different positions) or the
mecA
promoter (two different positions), while a 28-base deletion in
mecI
was found in one strain. In contrast, no mutation was detected in these gene sequences of MRSE strains.
Antiproliferative and Apoptotic Activities of Ketonucleosides and Keto-C-Glycosides against Non-Small-Cell Lung Cancer Cells with Intrinsic Drug Resistance
Authors: Paterson Jesse , Uriel Clara , Egron Marie-Jose , Herscovici Jean , Antonakis Kostas , Alaoui-Jamali Moulay A. 
Published: October 2018

ABSTRACT
We compared the biological activity of a new group of keto-C-glycosides to that of a narrow spectrum of unsaturated ketonucleosides in a panel of non-small-cell lung cancer (NSCLC) cells with various levels of intrinsic resistance to standard chemotherapy drugs. Unlike cisplatin, etoposide, adriamycin, or taxol, for which a significant difference in the cytotoxic effect was observed between sensitive cell lines (H460, H125, and MGH4) and drug-resistant cell lines (H661, MGH7, and FADU), nucleoside analogs were equally cytotoxic in NSCLC cell lines, with compound 92 being 10-fold more active than compound 43, 44, 81, or 161, while compound 3 was the least active. Apoptotic measurements with flow cytometric analysis of terminal uridine deoxynucleotide nick end-labeled cells revealed that the cytotoxic activity of these nucleosides correlated with their potency to induce apoptosis. Compound 92 triggered death in cells with wild-type p53, mutated p53, or p53 gene deletion. Our findings suggest that keto-C-glycosides may be promising alternative anticancer agents which merit further studies in in vivo cancer models refractory to standard chemotherapy drugs.
Discriminatory Detection of Inhibitor-Resistant β-Lactamases in
Escherichia coli
by Single-Strand Conformation Polymorphism-PCR
Authors: Speldooren Valérie , Heym Beate , Labia Roger , Nicolas-Chanoine Marie-Hélène 
Published: October 2018

ABSTRACT

Plasmid-mediated mechanisms, comprising TEM hyperproduction, TEM derivative production, and OXA production, lead to amoxicillin-clavulanic acid resistance in enterobacteria. The ability of the single-strand conformation polymorphism (SSCP)-PCR method to differentiate the genes encoding inhibitor-resistant β-lactamases was evaluated with three
bla
TEM
primer pairs. The
bla
TEM
genes, which were known to be different on the basis of their nucleotide sequences (
bla
TEM-1A
,
bla
TEM-1B
,
bla
TEM-2
,
bla
TEM-30
,
bla
TEM-32
, and
bla
TEM-35
), were identified as different by their electrophoretic mobilities. The
bla
TEM-33
,
bla
TEM-34
,
bla
TEM-36
,
bla
TEM-37
,
bla
TEM-38
, and
bla
TEM-39
genes, whose sequence differences have been established by oligotyping, displayed different SSCP profiles for different fragments, suggesting genetic differences in addition to those defined by oligotyping. Confirmed by sequencing, these additional genetic events concerned silent mutations at certain positions and, notably, a G→T transversion at position 1 of the −10 consensus sequence in
bla
TEM-34
,
bla
TEM-36
,
bla
TEM-37
, and
bla
TEM-39
. Applied to eight clinical isolates of
Escherichia coli
resistant to amoxicillin-clavulanic acid, the SSCP method detected TEM-1 in three strains and TEM-30, TEM-32, and TEM-35 in three other strains, respectively. A novel TEM derivative (TEM-58) was detected in another strain, and the deduced amino acid sequence showed two substitutions: Arg244Ser, which is known to confer amoxicillin-clavulanic acid resistance in TEM-30, and Val261Ile, which has not been described previously. The eighth strain produced an OXA β-lactamase. Given the discriminatory power and the applicability of SSCP-PCR, this method can be proposed as a means of following the evolution of the frequencies of the different inhibitor-resistant β-lactamases.
Activity of Voriconazole, a New Triazole, Combined with Neutrophils or Monocytes against
Candida albicans
: Effect of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Vora Shefali , Purimetla Nayanatara , Brummer Elmer , Stevens David A. 
Published: October 2018

ABSTRACT

The antifungal activity of voriconazole (VCZ) was tested against
Candida albicans
in the absence or presence of polymorphonuclear neutrophils (PMN) or monocytes. In some experiments, VCZ was compared to fluconazole (FCZ). On a weight basis, VCZ was 10-fold more efficacious than FCZ against
C. albicans
Sh27. Against an FCZ-resistant isolate, VCZ at 1 μg/ml produced the same fungistasis as FCZ at 20 μg/ml. VCZ at 0.1 μg/ml collaborated with PMN for enhanced killing to the same extent as FCZ at 1.0 μg/ml. Granulocyte-colony-stimulating factor (G-CSF) enhanced the candidacidal activity of PMN, and it increased the collaboration of PMN with VCZ for killing. Granulocyte-macrophage (GM)-CSF also significantly enhanced both the killing by PMN and the collaboration of PMN with VCZ for killing. VCZ collaborated with monocytes for enhanced killing of
C. albicans
Sh27, and GM-CSF increased this collaboration. Taken together, these data show that VCZ is more potent than FCZ against
C. albicans
isolates, alone and in collaboration with PMN or monocytes for enhanced killing. In addition, G-CSF- or GM-CSF-activated PMN and monocytes have enhanced collaboration with VCZ compared to that of unstimulated phagocytes with VCZ.
Effect of Grapefruit Juice on Clarithromycin Pharmacokinetics
Authors: Cheng Kit L. , Nafziger Anne N. , Peloquin Charles A. , Amsden Guy W. 
Published: October 2018

ABSTRACT

To investigate whether grapefruit juice inhibits the metabolism of clarithromycin, 12 healthy subjects were given water or grapefruit juice before and after a clarithromycin dose of 500 mg in a randomized crossover study. Administration of grapefruit juice increased the time to peak concentration of both clarithromycin (82 ± 35 versus 148 ± 83 min;
P
= 0.02) and 14-hydroxyclarithromycin (84 ± 38 min versus 173 ± 85;
P
= 0.01) but did not affect other pharmacokinetic parameters.
Comparative In Vitro Killing Activities of Meropenem, Imipenem, Ceftriaxone, and Ceftriaxone plus Vancomycin at Clinically Achievable Cerebrospinal Fluid Concentrations against Penicillin-Resistant
Streptococcus pneumoniae
Isolates from Children with Meningitis
Authors: Fitoussi Frederic , Doit Catherine , Benali Karim , Bonacorsi Stephane , Geslin Pierre , Bingen Edouard 
Published: October 2018

ABSTRACT

The activities of meropenem, imipenem, ceftriaxone, and vancomycin were evaluated against 80 penicillin-susceptible and -resistant
Streptococcus pneumoniae
strains. Meropenem, imipenem, ceftriaxone, and vancomycin MICs at which 90% of the isolates are inhibited were 0.5, 0.25, 1, and 0.25 μg/ml, respectively. Against penicillin-resistant strains, the best killing activity at cerebrospinal fluid concentrations was obtained with imipenem and ceftriaxone-vancomycin. However, while the killing activity of imipenem was significantly greater than that of meropenem, no significant difference was observed between the activities of meropenem and ceftriaxone-vancomycin.
Antipneumococcal Activities of a Ketolide (HMR 3647), a Streptogramin (Quinupristin-Dalfopristin), a Macrolide (Erythromycin), and a Lincosamide (Clindamycin)
Authors: Barry A. L. , Fuchs P. C. , Brown S. D. 
Published: October 2018

ABSTRACT

Four different compounds belonging to the macrolide-lincosamide-streptogramin B (MLS
b
) class of antimicrobial agents were tested against 611
Streptococcus pneumoniae
strains. The ketolide (HMR 3647, previously RU66647) and the streptogramin (quinupristin-dalfopristin) were both active against pneumococci with high-level MLS
b
resistance (clindamycin-resistant strains) as well as those with low-level macrolide resistance (clindamycin-susceptible strains).
In Vitro and In Vivo Antidermatophyte Activities of NND-502, a Novel Optically Active Imidazole Antimycotic Agent
Authors: Niwano Yoshimi , Kuzuhara Naoki , Kodama Hiroki , Yoshida Masanori , Miyazaki Tsuneo , Yamaguchi Hideyo 
Published: October 2018

ABSTRACT

In vitro and in vivo antidermatophyte activities of NND-502, a new imidazole antimycotic agent, were compared with those of two existing antifungal agents, lanoconazole and terbinafine. NND-502 exhibited strong in vitro antifungal activity against
Trichophyton
spp.; its MIC was 1 to 4 times lower than that of lanoconazole or terbinafine. In an in vivo study with a guinea pig model of tinea pedis, 7-day topical treatment with a 0.5% solution of NND-502 (dissolved in polyethylene glycol 400) was more effective than that with a 0.5% solution of either lanoconazole or terbinafine for eradicating fungi from the infected feet. When the duration of treatment was shortened to 3 days, a topical 1% solution of NND-502 achieved a complete mycological cure, while topical 1% solutions of lanoconazole and terbinafine did not.
In Vitro Antimicrobial Activity of MSI-78, a Magainin Analog
Authors: Fuchs Peter C. , Barry Arthur L. , Brown Steven D. 
Published: October 2018

ABSTRACT

MSI-78 is a cationic peptide with broad-spectrum antimicrobial activity and is being developed as a topical agent. We compared the in vitro activity of MSI-78 with those of ofloxacin and other antibiotics against fresh clinical isolates. Based on MIC distribution statistics, strains for which the MSI-78 MIC was ≤64 μg/ml were assumed to be susceptible for purposes of this report. Of 411 aerobic isolates tested, 91% were susceptible to MSI-78, compared to 91% for ofloxacin and 92% for ciprofloxacin. Only enterococci consistently required ≥64 μg of MSI-78/ml for inhibition. MSI-78 demonstrated bactericidal activity equivalent to that of ofloxacin. Of 61 anaerobes, 97% were susceptible to MSI-78. Of 10 isolates of
Candida albicans
, 3 were inhibited by MSI-78 at 24 h. Further studies of this compound appear to be warranted.
Characterization of
grlA
,
grlB
,
gyrA
, and
gyrB
Mutations in 116 Unrelated Isolates of
Staphylococcus aureus
and Effects of Mutations on Ciprofloxacin MIC
Authors: Schmitz Franz-Josef , Jones Mark E. , Hofmann Basia , Hansen Birgit , Scheuring Sibylle , Lückefahr Marc , Fluit Ad , Verhoef Jan , Hadding Ulrich , Heinz Hans-Peter , Köhrer Karl 
Published: October 2018

ABSTRACT

One hundred sixteen unrelated clinical isolates of
Staphylococcus aureus
(70 ciprofloxacin resistant and 46 ciprofloxacin susceptible) from eight countries were studied for the presence of mutations in the
grlA
,
grlB
,
gyrA
, and
gyrB
gene loci. Two mutations within
grlA
(located at codons 80 and 84) and two mutations within
gyrA
(located at codons 84 and 88) were clearly associated with ciprofloxacin resistance, although other mutations detected within the four genes studied may also contribute to decreased susceptibility.
Assessment of the Effects of Combination Therapy with Ciprofloxacin and Fenbufen on the Central Nervous Systems of Healthy Volunteers by Quantitative Electroencephalography
Authors: Kamali F. , Ashton C. H. , Marsh V. R. , Cox J. 
Published: October 2018

ABSTRACT
The potential effects of concurrent administration of fenbufen and ciprofloxacin on central nervous system activity in healthy young subjects were investigated by electroencephalography (EEG). Visual analog scales (VAS) were used to assess subjective measures of concentration, vigilance, tension, and irritability. When ciprofloxacin was administered in combination with fenbufen, none of the EEG parameters or VAS ratings measured were significantly different from those measured when the drugs were administered alone.
In Vitro Antimicrobial Effects of Various Combinations of Penicillin and Clindamycin against Four Strains of
Streptococcus pyogenes
Authors: Stevens Dennis L. , Madaras-Kelly Karl J. , Richards David M. 
Published: October 2018

ABSTRACT

Previous studies using mouse models of
Streptococcus pyogenes
necrotizing fasciitis demonstrated that clindamycin had greater efficacy than penicillin. Frequently both agents are used concurrently in the treatment of severe
S. pyogenes
infections. This study investigated interactions between penicillin and clindamycin. E-test and broth microdilution assays suggested additivity or indifference, while timed-killing assays demonstrated concentration-dependent variable effects. Timed-kill studies utilizing clinical concentrations suggest that there is no antagonism with the combination of drugs but that the combination does not have a bactericidal advantage over either penicillin or clindamycin alone.
Susceptibilities of Neonatal Respiratory Isolates of
Ureaplasma urealyticum
to Antimicrobial Agents
Authors: Matlow Anne , Th’ng Cecilia , Kovach Danuta , Quinn Patricia , Dunn Michael , Wang Elaine 
Published: October 2018

ABSTRACT

Twenty-one neonatal respiratory isolates of
Ureaplasma urealyticum
were serotyped, and their susceptibilities to ciprofloxacin, gentamicin, chloramphenicol, erythromycin, azithromycin, and doxycycline were tested. Most patient strains were
Ureaplasma urealyticum
bv. parvum. Chloramphenicol, doxycycline, and azithromycin had the lowest MICs. This data may be useful when designing prophylactic or therapeutic trials of antibiotics for chronic lung disease of the newborn.
Pharmacokinetic Studies of Fluconazole in Rabbits Characterizing Doses Which Achieve Peak Levels in Serum and Area under the Concentration-Time Curve Values Which Mimic Those of High-Dose Fluconazole in Humans
Authors: Louie Arnold , Liu Qing-Feng , Drusano George L. , Liu Weiguo , Mayers Martin , Anaissie Elias , Miller Michael H. 
Published: October 2018

ABSTRACT
We conducted steady-state pharmacokinetic studies with high-dose fluconazole with rabbits and human volunteers. We then derived mathematical equations that predict the doses of fluconazole that should be given to rabbits to produce 24-h area under the concentration-time curve values and maximum concentrations in serum that are similar to those measured for humans given 800 to 2,000 mg of fluconazole per day. These equations provide a rational basis for designing future efficacy studies with rabbits and in evaluating the strength with which results of previously conducted studies using rabbit infection models can be extrapolated to the clinic.
Inhibition of Hyphal Growth of Azole-Resistant Strains of
Candida albicans
by Triazole Antifungal Agents in the Presence of Lactoferrin-Related Compounds
Authors: Wakabayashi Hiroyuki , Abe Shigeru , Teraguchi Susumu , Hayasawa Hirotoshi , Yamaguchi Hideyo 
Published: October 2018

ABSTRACT

The effects of bovine lactoferrin (LF) or the LF-derived antimicrobial peptide lactoferricin B (LFcin B) on the growth of
Candida albicans
hyphae, including those of three azole-resistant strains, were investigated by a crystal violet staining method. The hyphae of two highly azole-resistant strains were more susceptible to inhibition by LF or LFcin B than the azole-susceptible strains tested. One moderately azole-resistant strain was defective in the formation of hyphae and showed a susceptibility to LF greater than that of the susceptible strains but a susceptibility to LFcin B similar to that of the susceptible strains. The highly azole-resistant strain TIMM3317 showed trailing growth in the presence of fluconazole or itraconazole, while the extent of growth was reduced by the addition of LF or LFcin B at a sub-MIC. Thus, the addition of LF or LFcin B at a sub-MIC resulted in a substantial decrease in the MICs of fluconazole and itraconazole for two highly azole-resistant strains; e.g., the MIC of fluconazole for TIMM3317 was shifted from >256 to 0.25 μg/ml by LF, but the MICs were not decreased for the susceptible strains. The combination effects observed with triazoles and LF-related compounds in the case of the two highly azole-resistant strains were confirmed to be synergistic by the fractional inhibitory concentration index. These results demonstrate that for some azole-resistant
C. albicans
strains, LF-related compounds combined with triazoles can inhibit the growth of hyphae, an important form of this organism in pathogenesis.
Susceptibility of
Chlamydia trachomatis
to Chlorhexidine Gluconate Gel
Authors: Lampe M. F. , Ballweber L. M. , Stamm W. E. 
Published: October 2018

ABSTRACT

To identify topical antimicrobial preparations which may be effective in preventing the transmission of sexually transmitted diseases, we examined the activity of chlorhexidine gluconate (CHG) against
Chlamydia trachomatis
. Chlamydial elementary bodies were incubated with dilutions of CHG gel for various times from 0 to 120 min. An aliquot of each dilution was further diluted and was inoculated onto McCoy cell monolayers in individual wells in a 96-well microtiter plate. The cultures were incubated for 48 h, and the chlamydial inclusions were stained and counted. CHG gel diluted fourfold (0.0625% CHG) killed
C. trachomatis
serovar D, and CHG gel diluted eightfold (0.0313% CHG) killed serovar F immediately upon exposure. CHG gel diluted 16-fold (0.0156% CHG) killed serovar D, and CHG gel diluted 32-fold (0.0078% CHG) killed serovar F after 120 min of exposure. Alteration of the pH over the range of from 4 to 8 did not significantly affect its activity. The addition of 10% whole human blood decreased the CHG gel activity at 0 min but had no significant effect after 120 min of exposure. We conclude that CHG gel may be effective topically against
C. trachomatis
at concentrations that can be used and under conditions that are found in the female genital tract and that further studies of its antimicrobial efficacy and toxicity in vivo are warranted.
NADPH Cytochrome P-450 Oxidoreductase and Susceptibility to Ketoconazole
Authors: Venkateswarlu K. , Kelly Diane E. , Manning Nigel J. , Kelly Steven L. 
Published: October 2018

ABSTRACT

The phenotype of a strain of
Saccharomyces cerevisiae
containing a disruption of the gene encoding NADPH cytochrome P-450 oxidoreductase (
CPR
) was quantified biochemically and microbiologically, as were those of various transformants of this strain after expression of native CPR, cytochrome P-45051 (CYP51), and a fusion protein of CYP51-CPR (FUS). Only a 4-fold decrease in ergosterol biosynthesis was observed for the
cpr
strain, but ketoconazole sensitivity increased 200-fold, indicating hypersensitivity to the alternative electron donor system in
cpr
strains. Both phenotypes could be reversed in transformants expressing the CPR and FUS, indicating the availability of the CPR in FUS as well as the expressed native CPR for monoxygenase-associated reactions. The complementation of function was observed both in vitro and in vivo for the monoxygenases squalene epoxidase, CYP51, and CYP61 in the ergosterol biosynthesis pathway with which CPR is coupled. Overexpression of CYP51 and FUS produced different levels of ketoconazole resistance in wild-type cells, indicating that the availability of CPR may limit the potential of overproduction of CYP51 as a mechanism of resistance to azole antifungal agents.