bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Inactivation of
Chlamydia trachomatis
by Fatty Acids and Monoglycerides
Authors: Bergsson Gudmundur , Arnfinnsson Jóhann , Karlsson Sigfús M. , Steingrímsson Ólafur , Thormar Halldor 
Published: October 2018

ABSTRACT

The antichlamydial effects of several fatty acids and monoglycerides were studied by incubating
Chlamydia trachomatis
bacteria with equal volumes of lipid solutions for 10 min and measuring the reduction in infectivity titer compared with that in a control solution without lipid. Caprylic acid (8:0), monocaprylin (8:0), monolaurin (12:0), myristic acid (14:0), palmitoleic acid (16:1), monopalmitolein (16:1), oleic acid (18:1), and monoolein (18:1) at concentrations of 20 mM (final concentration, 10 mM) had negligible effects on
C. trachomatis
. In contrast, lauric acid (12:0), capric acid (10:0), and monocaprin (10:0) caused a greater than 10,000-fold (>4-log
10
) reduction in the infectivity titer. When the fatty acids and monoglycerides were further compared at lower concentrations and with shorter exposure times, lauric acid was more active than capric acid and monocaprin was the most active, causing a greater than 100,000-fold (>5-log
10
) inactivation of
C. trachomatis
at a concentration of 5 mM for 5 min. The high levels of activity of capric and lauric acids and particularly that of monocaprin are notable and suggest that these lipids have specific antichlamydial effects. The mode of action of monocaprin was further studied by removal of the lipid by centrifugation before inoculation of
Chlamydia
onto host cells and by electron microscopy. The results indicate that the bacteria are killed by the lipid, possibly by disrupting the membrane(s) of the elementary bodies. A 50% effective concentration of 30 μg/ml was found by incubation of
Chlamydia
with monocaprin for 2 h. The rapid inactivation of large numbers of
C. trachomatis
organisms by monocaprin suggests that it may be useful as a microbicidal agent for the prevention of the sexual transmission of
C. trachomatis
.
Effect of Food on the Bioavailability of Stavudine in Subjects with Human Immunodeficiency Virus Infection
Authors: Kaul Sanjeev , Christofalo Barbara , Raymond Ralph H. , Stewart Michael B. , Macleod Catherine M. 
Published: October 2018

ABSTRACT

A randomized, three-way crossover study was carried out to determine the effects of food ingestion on the pharmacokinetics of stavudine (d4T). Fifteen subjects with human immunodeficiency virus (HIV) infection and CD4
+
cell counts of ≥200/μl received 70 mg of d4T in a fasting state or 1 h before or 5 min after a standardized high-fat breakfast. A 7- to 15-day washout period was included between treatments. Blood and urine were collected before and for 10 h after dosing, and plasma and urine d4T concentrations were determined with a validated radioimmunoassay. Plasma drug concentration-time data were analyzed with a noncompartmental model. The mean maximum plasma drug concentration (
C
max
) and the time to
C
max
(
T
max
) for administration of d4T after a meal were significantly lower and longer (
P
= 0.0001 for both measures) than those observed in the fasting state, although the area under the concentration-time curve from time zero to infinity (AUC
0–∞
) was not significantly different. Neither of these parameters was significantly altered when d4T was taken 1 h before a meal. The bioavailability of d4T taken after a meal was 95% of that observed in the fasting state, and it was 97% when d4T was administered before a meal (
P
> 0.05 for both comparisons with the fasting state). The results of this study indicate that (i) ingestion of food does not affect the bioavailability of d4T and that patients with HIV infection can take it without regard to meals, and (ii) absorption is essentially complete within 1 h when d4T is administered in the fasted state.
Activity of Voriconazole Combined with Neutrophils or Monocytes against
Aspergillus fumigatus
: Effects of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Vora Shefali , Chauhan Sharda , Brummer Elmer , Stevens David A. 
Published: October 2018

ABSTRACT

Voriconazole (VCZ) was tested for antifungal activity against
Aspergillus fumigatus
hyphae alone or in combination with neutrophils or monocytes. Antifungal activity was measured as percent inhibition of hyphal growth in assays using the dye MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] or XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2
H
-tetrazolium-5-carboxanilide]. With both assays, VCZ inhibited hyphal growth at concentrations of <1 μg/ml and was almost as active as amphotericin B. VCZ (0.6 μg/ml) was sporicidal, as was amphotericin B (0.4 μg/ml). With both the MTT and XTT assays, neutrophils alone inhibited hyphae; when combined with VCZ, there was additive activity. Both granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated polymorphonuclear neutrophils (PMN) had enhanced inhibition of hyphal growth. Moreover, such treatment of PMN also enhanced the collaboration of PMN with VCZ. Monocytes inhibited hyphal growth. When VCZ was combined with monocytes or monocytes were treated with GM-CSF, inhibition was significantly increased, to similar levels. However, the combination of VCZ with GM-CSF treatment of monocytes did not significantly increase the high-level inhibition by monocytes with either agent alone.
Pharmacokinetics of Meropenem in Critically Ill Patients with Acute Renal Failure Treated by Continuous Hemodiafiltration
Authors: Krueger W. A. , Schroeder T. H. , Hutchison M. , Hoffmann E. , Dieterich H.-J. , Heininger A. , Erley C. , Wehrle A. , Unertl K. 
Published: October 2018

ABSTRACT
The pharmacokinetics of meropenem were studied in nine anuric critically ill patients treated by continuous venovenous hemodiafiltration. Peak levels after infusion of 1,000 mg over 30 min amounted to 103.2 ± 45.9 μg/ml, and trough levels at 12 h were 9.6 ± 3.8 μg/ml. A dosage of 1,000 mg of meropenem twice a day provides plasma drug levels covering intermediately susceptible microorganisms. Further reductions of the dosage might be appropriate for highly susceptible bacteria or when renal replacement therapies with lower clearances are applied.
Prevalence and Characterization of the Mechanisms of Macrolide, Lincosamide, and Streptogramin Resistance in Isolates of
Streptococcus pneumoniae
Authors: Johnston Nicole J. , de Azavedo Joyce C. , Kellner James D. , Low Donald E. 
Published: October 2018

ABSTRACT

Of a total of 147 erythromycin-resistant
Streptococcus pneumoniae
isolates, 64 (43.5%) were resistant to erythromycin, clindamycin, and streptogramin B (MLS
B
phenotype), 57 of which possessed the
ermB
gene. Eighty-two (55.8%) were resistant to erythromycin alone (M phenotype), 81 of which possessed the
mefE
gene. One was erythromycin and streptogramin B resistant but susceptible to clindamycin (MS phenotype) and possessed neither the
erm
gene nor the
mefE
gene.
Uptake and Intracellular Activity of Moxifloxacin in Human Neutrophils and Tissue-Cultured Epithelial Cells
Authors: Pascual Alvaro , García Isabel , Ballesta Sofía , Perea Evelio J. 
Published: October 2018

ABSTRACT

The penetration by moxifloxacin of human neutrophils (polymorphonuclear leukocytes [PMN]) and tissue-cultured epithelial cells (McCoy cells) was evaluated by a fluorometric assay. At extracellular concentrations of 5 mg/liter, the cellular-to-extracellular concentration ratios (C/E) of moxifloxacin in PMN and McCoy cells were 10.9 ± 1.0 and 8.7 ± 1.0, respectively (20 min; 37°C). The uptake of moxifloxacin by PMN was rapid, reversible, nonsaturable (at extracellular concentrations ranging from 1 to 50 μg/ml), and not affected by cell viability. The uptake of moxifloxacin was affected by external pH and the environmental temperature. The incubation of PMN in the presence of sodium fluoride, sodium cyanide, and carbonyl cyanide
m
-chlorophenylhydrazone significantly decreased the C/E of this agent. Neither PMN stimulation nor phagocytosis of opsonized
Staphylococcus aureus
significantly affected the uptake of moxifloxacin by human PMN. This agent, at concentrations of 0.5, 1, and 5 mg/liter, induced a significant reduction in the survival of intracellular
S. aureus
in human PMN. In summary, moxifloxacin reaches much higher intracellular concentrations within phagocytic and nonphagocytic cells than extracellular ones, remaining active inside the neutrophils.
Efficacy of New 5-Nitroimidazoles against Metronidazole-Susceptible and -Resistant
Giardia
,
Trichomonas
, and
Entamoeba
spp
Authors: Upcroft Jacqueline A. , Campbell Raymond W. , Benakli Kamel , Upcroft Peter , Vanelle Patrice 
Published: October 2018

ABSTRACT

The efficacies of 12 5-nitroimidazole compounds and 1 previously described lactam-substituted nitroimidazole with antiparasitic activity, synthesized via S
RN
1 and subsequent reactions, were assayed against the protozoan parasites
Giardia duodenalis
,
Trichomonas vaginalis
, and
Entamoeba histolytica
. Two metronidazole-sensitive lines and two metronidazole-resistant lines of
Giardia
and one line each of metronidazole-sensitive and -resistant
Trichomonas
were tested. All except one of the compounds were as effective or more effective than metronidazole against
Giardia
and
Trichomonas
, but none was as effective overall as the previously described 2-lactam-substituted 5-nitroimidazole. None of the compounds was markedly more effective than metronidazole against
Entamoeba
. Significant cross-resistance between most of the drugs tested and metronidazole was evident among metronidazole-resistant lines of
Giardia
and
Trichomonas
. However, some drugs were lethal to metronidazole-resistant
Giardia
and had minimum lethal concentrations similar to that of metronidazole for drug-susceptible parasites. This study emphasizes the potential in developing new nitroimidazole drugs which are more effective than metronidazole and which may prove to be useful clinical alternatives to metronidazole.
Efficacy of Trovafloxacin in Treatment of Experimental Staphylococcal or Streptococcal Endocarditis
Authors: Entenza J. M. , Vouillamoz J. , Glauser M. P. , Moreillon P. 
Published: October 2018

ABSTRACT

The efficacy of trovafloxacin against
Staphylococcus aureus
and viridans group streptococci was investigated in vitro and in an experimental model of endocarditis. The MICs at which trovafloxacin and ciprofloxacin inhibited 90% of clinical isolates of such bacteria (MIC
90
s) were (i) 0.03 and 2 mg/liter, respectively, for 30 ciprofloxacin-susceptible
S. aureus
isolates, (ii) 32 and 128 mg/liter, respectively, for 20 ciprofloxacin-resistant
S. aureus
isolates, and (iii) 0.25 and 8 mg/liter, respectively, for 28 viridans group streptococci. Rats with aortic vegetations were infected with either of two ciprofloxacin-susceptible but methicillin-resistant
S. aureus
strains (strains COL and P8), one penicillin-susceptible
Streptococcus sanguis
strain, or one penicillin-resistant
Streptococcus mitis
strain. Rats were treated for 3 or 5 days with doses that resulted in kinetics that simulated those achieved in humans with trovafloxacin (200 mg orally once a day), ciprofloxacin (750 mg orally twice a day), vancomycin (1 g intravenously twice a day), or ceftriaxone (2 g intravenously once a day). Against the staphylococci, the activities of both trovafloxacin and ciprofloxacin were equivalent to that of vancomycin, and treatment of endocarditis with these drugs was successful (
P
< 0.05). However, ciprofloxacin selected for resistant derivatives in vitro and in vivo, whereas trovafloxacin was 10 to 100 times less prone than ciprofloxacin to select for resistance in vitro and did not select for resistance in vivo. Against the two streptococcal isolates, trovafloxacin significantly (
P
< 0.05) decreased bacterial counts in the vegetations but was less effective than the control drug, ceftriaxone. Thus, a simulated oral dose of trovafloxacin (200 mg per day) was effective against ciprofloxacin-susceptible staphylococci and was less likely than ciprofloxacin to select for resistance. The simulated oral dose of trovafloxacin also had some activity against streptococcal endocarditis, but optimal treatment of infections caused by such organisms might require higher doses of the drug.
In Vitro Activity of the Ketolide HMR 3647 (RU 6647) for
Legionella
spp., Its Pharmacokinetics in Guinea Pigs, and Use of the Drug To Treat Guinea Pigs with
Legionella pneumophila
Pneumonia
Authors: Edelstein Paul H. , Edelstein Martha A. C. 
Published: October 2018

ABSTRACT

The activities of HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin for 97
Legionella
spp. isolates were determined by microbroth dilution susceptibility testing. Growth inhibition of two
Legionella pneumophila
strains grown in guinea pig alveolar macrophages was also determined. The concentrations required to inhibit 50% of strains tested were 0.06, 0.02, 0.25, 0.03, and 0.02 μg/ml for HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin, respectively. BYEα broth did not significantly inhibit the activities of the drugs tested, as judged by the susceptibility of the control
Staphylococcus aureus
strain; however, when
Escherichia coli
was used as the test strain, levofloxacin activity tested in BYEα broth was fourfold lower. HMR 3647, HMR 3004, erythromycin, and clarithromycin (0.25 and 1 μg/ml) reduced bacterial counts of two
L. pneumophila
strains grown in guinea pig alveolar macrophages by 0.5 to 1 log
10
, but regrowth occurred over a 2-day period. HMR 3647, erythromycin, and clarithromycin appeared to have equivalent intracellular activities which were solely static in nature. HMR 3004 was more active than all drugs tested except levofloxacin. In contrast, levofloxacin (1 μg/ml) was bactericidal against intracellular
L. pneumophila
and significantly more active than the other drugs tested. Therapy studies with HMR 3647 and erythromycin were performed in guinea pigs with
L. pneumophila
pneumonia. When HMR 3647 was given (10 mg/kg of body weight) by the intraperitoneal route to infected guinea pigs, mean peak plasma levels were 1.4 μg/ml at 0.5 h and 1.0 μg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.4 h. All 16
L. pneumophila
-infected guinea pigs treated with HMR 3647 (10 mg/kg/dose given intraperitoneally once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of HMR 3647 given twice daily. Fourteen of 16 erythromycin-treated (30 mg/kg/dose given intraperitoneally twice daily) animals survived, whereas 0 of 12 animals treated with saline survived. HMR 3647 is effective against
L. pneumophila
in vitro, in infected macrophages, and in a guinea pig model of Legionnaires’ disease. HMR 3647 given once daily should be evaluated as a treatment for Legionnaires’ disease in humans.
Killing Activities of Trovafloxacin Alone and in Combination with β-Lactam Agents, Rifampin, or Vancomycin against
Streptococcus pneumoniae
Isolates with Various Susceptibilities to Extended-Spectrum Cephalosporins at Concentrations Clinically Achievable in Cerebrospinal Fluid
Authors: Fitoussi Frederic , Doit Catherine , Geslin Pierre , Bingen Edouard 
Published: October 2018

ABSTRACT

The killing activities of trovafloxacin alone and in combination with β-lactam agents (extended-spectrum cephalosporins, meropenem), rifampin, or vancomycin were evaluated against 20 genotypically characterized
Streptococcus pneumoniae
isolates for which amoxicillin MICs were ≥4 μg/ml (cefotaxime MICs, ≥4 μg/ml for six strains) at concentrations clinically achievable in cerebrospinal fluid. At 6 h the mean killing activity of trovafloxacin alone (range, 2.6 to 2.9 log
10
CFU/ml) did not vary significantly according to the susceptibility of the strains to β-lactam agents. The activities of trovafloxacin or vancomycin added to the β-lactam agents and the combination trovafloxacin-vancomycin were additive or indifferent. Against the ceftriaxone-resistant isolates, the killing activity of the combination of a β-lactam agent and trovafloxacin did not differ significantly from that of a β-lactam agent and vancomycin.
Molecular Cloning of the
gyrA
and
gyrB
Genes of
Bacteroides fragilis
Encoding DNA Gyrase
Authors: Onodera Yoshikuni , Sato Kenichi 
Published: October 2018

ABSTRACT

The genes encoding the DNA gyrase A and B subunits of
Bacteroides fragilis
were cloned and sequenced. The
gyrA
and
gyrB
genes code for proteins of 845 and 653 amino acids, respectively. These proteins were expressed in
Escherichia coli
, and the combination of GyrA and GyrB exhibited ATP-dependent supercoiling activity. To analyze the role of DNA gyrase in quinolone resistance of
B. fragilis
, we isolated mutant strains by stepwise selection for resistance to increasing concentrations of levofloxacin. We analyzed the resistant mutants and showed that Ser-82 of GyrA, equivalent to resistance hot spot Ser-83 of GyrA in
E. coli
, was in each case replaced with Phe. These results suggest that DNA gyrase is an important target for quinolones in
B. fragilis.
Detection of Rifampin Resistance in
Mycobacterium tuberculosis
by Double Gradient-Denaturing Gradient Gel Electrophoresis
Authors: Scarpellini Paolo , Braglia Sergio , Carrera Paola , Cedri Maura , Cichero Paola , Colombo Alessia , Crucianelli Rosella , Gori Andrea , Ferrari Maurizio , Lazzarin Adriano 
Published: October 2018

ABSTRACT

We applied double gradient-denaturing gradient gel electrophoresis (DG-DGGE) for the rapid detection of rifampin (RMP) resistance from
rpoB
PCR products of
Mycobacterium tuberculosis
isolates and clinical samples. The results of this method were fully concordant with those of DNA sequencing and susceptibility testing analyses. DG-DGGE is a valid alternative to the other methods of detecting mutations for predicting RMP resistance.
Lipoprotein Distribution of a Novel Endotoxin Antagonist, E5531, in Plasma from Human Subjects with Various Lipid Levels
Authors: Wasan Kishor M. , Strobel Frank W. , Parrott Steven C. , Lynn Melvyn , Christ William J. , Hawkins Lynn D. , Rossignol Daniel P. 
Published: October 2018

ABSTRACTThe purpose of this study was to determine the distribution profile of a novel endotoxin antagonist, [14C]E5531, at 1 μg/ml in plasma samples obtained from fasted human subjects with various lipid and protein concentrations. Our findings suggest that the majority of E5531 binds with high-density lipoproteins (HDLs) independently of plasma lipid and protein levels tested. Furthermore, it appears that an increase in triglyceride-rich lipoprotein (TRL) lipid and protein levels and an increase in low-density lipoprotein (LDL) lipid levels significantly increase TRL plus LDL binding of E5531. However, only an increase in HDL protein levels significantly increases HDL binding of E5531.
Insertion of Mini-IS
605
and Deletion of Adjacent Sequences in the Nitroreductase (
rdxA
) Gene Cause Metronidazole Resistance in
Helicobacter pylori
NCTC11637
Authors: Debets-Ossenkopp Yvette J. , Pot Raymond G. J. , van Westerloo David J. , Goodwin Avery , Vandenbroucke-Grauls Christina M. J. E. , Berg Douglas E. , Hoffman Paul S. , Kusters Johannes G. 
Published: October 2018

ABSTRACT

We found that NCTC11637, the type strain of
Helicobacter pylori
, the causative agent of peptic ulcer disease and an early risk factor for gastric cancer, is metronidazole resistant. DNA transformation, PCR-based restriction analysis, and DNA sequencing collectively showed that the metronidazole resistance of this strain was due to mutation in
rdxA
(gene HP0954 in the full genome sequence of
H. pylori
26695) and that resistance did not depend on mutation in any of the other genes that had previously been suggested: catalase (
katA
), ferredoxin (
fdx
), flavodoxin (
fldA
), pyruvate:flavodoxin oxidoreductase (
por
γδαβ), RecA (
recA
), or superoxide dismutase (
sodB
). This is in accord with another recent study that attributed metronidazole resistance to point mutations in
rdxA
. However, the mechanism of
rdxA
inactivation that we found in NCTC11637 is itself also novel: insertion of mini-IS
605
, one of the endogenous transposable elements of
H. pylori
, and deletion of adjacent DNA sequences including 462 bp of the 851-bp-long
rdxA
gene.
High-Performance Liquid Chromatographic Determination of Ribavirin in Whole Blood To Assess Disposition in Erythrocytes
Authors: Homma Masato , Jayewardene Anura L. , Gambertoglio John , Aweeka Francesca 
Published: October 2018

ABSTRACT
Ribavirin is an antiviral agent used in the treatment of chronic hepatitis C virus infection. One of the limitations associated with the use of ribavirin is a reversible anemia caused by its accumulation in erythrocytes. Therefore, it is of interest to determine ribavirin levels in erythrocytes, as well as in plasma, as these measurements may be predictive of hematotoxicity. In the present study, we describe a high-performance liquid chromatographic (HPLC) assay for ribavirin in whole blood to estimate concentrations of free ribavirin and phosphorylated anabolites in erythrocytes. Since ribavirin exists primarily as phosphorylated anabolites (mono-, di-, and triphosphates) in erythrocytes, whole-blood extracts were initially dephosphorylated with acid phosphatase. The enzyme-treated samples were subjected to phenyl boronic acid column extraction for cleanup. The purified fraction was analyzed by reversed-phase HPLC, which was optimized for determination of ribavirin levels in whole blood. The recoveries of ribavirin from whole blood ranged from 63.1 to 90.7% at concentrations ranging from 1.67 to 40.0 μM. Intra- and interassay variations estimated at these concentrations were 3.2 to 10.4 and 4.7 to 11.7%, respectively. This method was used to quantitate ribavirin in samples both treated and untreated with acid phosphatase to estimate the extent of intracellular phosphorylation in erythrocytes. The method was also used to evaluate the effects of dipyridamole, a nucleoside transporter inhibitor, on ribavirin disposition in erythrocytes in in vitro experiments.