bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic Resistance of
Staphylococcus aureus
, Selected
Enterobacteriaceae
, and
Pseudomonas aeruginosa
after Single and Multiple In Vitro Exposures to Ciprofloxacin, Levofloxacin, and Trovafloxacin
Authors: Gilbert D. N. , Kohlhepp S. J. , Slama K. A. , Grunkemeier G. , Lewis G. , Dworkin R. J. , Slaughter S. E. , Leggett J. E. 
Published: July 2002

ABSTRACT

The phenotypic resistance of selected organisms to ciprofloxacin, levofloxacin, and trovafloxacin was defined as a MIC of ≥4 μg/ml. The dynamics of resistance were studied after single and sequential drug exposures: clinical isolates of methicillin-susceptible and methicillin-resistant
Staphylococcus aureus
(MSSA and MRSA),
Escherichia coli
,
Klebsiella pneumoniae
,
Enterobacter cloacae
,
Serratia marcescens
, and
Pseudomonas aeruginosa
were utilized. After a single 48-h exposure of a large inoculum to four times the initial MIC for the organism, the frequency of selection of resistant mutants of MSSA was greater for trovafloxacin than levofloxacin (
P
= 0.008); for
E. cloacae
, the frequency was highest for ciprofloxacin and lowest for levofloxacin and trovafloxacin; for
S. marcescens
, the frequency was highest for trovafloxacin and lowest for ciprofloxacin (
P
= 0.003). The results of serial passage experiments were analyzed both by the Kaplan-Meier product-limited method as well as by analysis of variance of mean inhibitory values. By both methods, MSSA and MRSA expressed mutants resistant to ciprofloxacin after fewer passages than were required for either levofloxacin or trovafloxacin. For the aerobic gram-negative bacilli, two general patterns emerged. Mutants resistant to trovafloxacin appeared sooner and reached higher mean MICs than did mutants resistant to levofloxacin or ciprofloxacin. Mutants resistant to ciprofloxacin appeared later and reached mean MICs lower than the MICs of the other two drugs studied. Even though individual strain variation occurred, the mean MICs were reproduced when the serial passage experiment was repeated using an identical panel of
E. coli
isolates. In summary, the dynamic selection of fluoroquinolone-resistant bacteria can be demonstrated in experiments that employ serial passage of bacteria in vitro.
Katanosin B and Plusbacin A
3
, Inhibitors of Peptidoglycan Synthesis in Methicillin-Resistant
Staphylococcus aureus
Authors: Maki Hideki , Miura Kenji , Yamano Yoshinori 
Published: July 2002

ABSTRACT

Both katanosin B and plusbacin A
3
are naturally occurring cyclic depsipeptide antibiotics containing a lactone linkage. They showed strong antibacterial activity against methicillin-resistant
Staphylococcus aureus
and VanA-type vancomycin-resistant enterococci, with MICs ranging from 0.39 to 3.13 μg/ml, as well as against other gram-positive bacteria. They inhibited the incorporation of
N
-acetylglucosamine, a precursor of cell wall synthesis, into peptidoglycan of
S. aureus
whole cells at concentrations close to their MICs. In vitro studies with a wall-membrane particulate fraction of
S. aureus
showed that katanosin B and plusbacin A
3
inhibited the formation of lipid intermediates, with 50% inhibitory concentrations (IC
50
s) of 2.2 and 2.3 μg/ml, respectively, and inhibited the formation of nascent peptidoglycan, with IC
50
s of 0.8 and 0.4 μg/ml, respectively. Vancomycin, a well-known inhibitor of transglycosylation, did not inhibit the formation of lipid intermediates but did inhibit the formation of nascent peptidoglycan, with an IC
50
of 4.1 μg/ml. Acetyl-Lys-
d
-Ala-
d
-Ala, an analog of the terminus of the lipid intermediates, effectively suppressed the inhibition of transglycosylation by vancomycin, but did not suppress those by katanosin B and plusbacin A
3
. These results indicate that the antibacterial activity of katanosin B and plusbacin A
3
is due to blocking of transglycosylation and its foregoing steps of cell wall peptidoglycan synthesis via a mechanism differing from that of vancomycin.
Activities of Hexadecylphosphocholine (Miltefosine), AmBisome, and Sodium Stibogluconate (Pentostam) against
Leishmania donovani
in Immunodeficient
scid
Mice
Authors: Escobar Patricia , Yardley Vanessa , Croft Simon L. 
Published: July 2002

ABSTRACT

In both
scid
and BALB/c mouse-
Leishmania donovani
models, hexadecyphosphocholine (miltefosine) and AmBisome had similar levels of activity. In contrast, sodium stibogluconate (Pentostam) was significantly less active against
L. donovani
in
scid
mice than in BALB/c mice. The in vitro anti-leishmanial activity of miltefosine was similar in peritoneal macrophages derived from both
scid
and BALB/c mice, whereas Pentostam and AmBisome were significantly more active in the latter.
Comparative In Vitro Activity of ABT-773, a Novel Antibacterial Ketolide
Authors: Nilius A. M. , Bui M. H. , Almer L. , Hensey-Rudloff D. , Beyer J. , Ma Z. , Or Y. S. , Flamm R. K. 
Published: July 2002

ABSTRACT

The in vitro activities of ABT-773, erythromycin, clarithromycin, and azithromycin were compared. ABT-773 was the most active compound against macrolide-susceptible
Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes
, and
Enterococcus
spp. and multidrug-resistant
Streptococcus pneumoniae
. It also had good activity against gram-negative and atypical respiratory tract pathogens and
Helicobacter pylori.
Identification of a Plasmid Encoding SHV-12, TEM-1, and a Variant of IMP-2 Metallo-β-Lactamase, IMP-8, from a Clinical Isolate of
Klebsiella pneumoniae
Authors: Yan Jing-Jou , Ko Wen-Chien , Wu Jiunn-Jong 
Published: July 2002

ABSTRACT

A multidrug-resistant plasmid encoding TEM-1, SHV-12, and a variant of IMP-2 metallo-β-lactamase, designated IMP-8, was identified from a clinical isolate of
Klebsiella pneumoniae
. There are four nucleotide differences between
bla
IMP-2
and
bla
IMP-8
, resulting in two amino acid differences.
bla
IMP-8
was also found to be carried by an integron-borne gene cassette similar to the
bla
IMP-2
cassette.
Influence of Liposomal Amphotericin B on CD8 T-Cell Function
Authors: Kretschmar Marianne , Geginat Gernot , Bertsch Thomas , Walter Simon , Hof Herbert , Nichterlein Thomas 
Published: July 2002

ABSTRACTLiposomal amphotericin B was immunosuppressive on target cell lysis in vitro and on protection mediated by cytotoxic CD8 T cells in murine listeriosis. When dosages usually used for therapy in humans were compared, the immunosuppressive effect of 5 mg of liposomal amphotericin B/kg of body weight/day was similar to that of standard amphotericin B at 1 mg/kg/day, but a dosage of liposomal amphotericin B of 1 mg/kg/day was not suppressive in vivo.
Cell-Based Fluorescence Assay for Human Immunodeficiency Virus Type 1 Protease Activity
Authors: Lindsten Kristina , Uhlı́ková Tat'ána , Konvalinka Jan , Masucci Maria G. , Dantuma Nico P. 
Published: July 2002

ABSTRACT
The human immunodeficiency virus type 1 (HIV-1) protease is essential for production of infectious virus and is therefore a major target for the development of drugs against AIDS. Cellular proteins are also cleaved by the protease, which explains its cytotoxic activity and the consequent failure to establish convenient cell-based protease assays. We have exploited this toxicity to develop a new protease assay that relies on transient expression of an artificial protease precursor harboring the green fluorescent protein (GFP-PR). The precursor is activated in vivo by autocatalytic cleavage, resulting in rapid elimination of protease-expressing cells. Treatment with therapeutic doses of HIV-1 protease inhibitors results in a dose-dependent accumulation of the fluorescent precursor that can be easily detected and quantified by flow cytometric and fluorimetric assays. The precursor provides a convenient and noninfectious model for high-throughput screenings of substances that can interfere with the activity of the protease in living cells.
Treatment of Visceral Leishmaniasis with Sterically Stabilized Liposomes Containing Camptothecin
Authors: Proulx Marie-Eve , Désormeaux André , Marquis Jean-François , Olivier Martin , Bergeron Michel G. 
Published: July 2002

ABSTRACT

The efficacy of 20(
S
)-camptothecin (CPT), free and incorporated into sterically stabilized liposomes, has been investigated in vitro against
Leishmania donovani
promastigotes and in vivo in a murine model of visceral leishmaniasis. Incubation of
L. donovani
promastigotes with free or liposomal CPT inhibited the growth of parasites in a dose-dependent manner. Tissue distribution studies revealed that the intraperitoneal administration of liposomal CPT was efficient for the delivery of high drug levels to the liver and spleen. Treatment of infected mice with intraperitoneal injections of free and liposomal CPT significantly reduced the parasite loads in the livers by 43 and 55%, respectively, compared with the loads for untreated controls. However, both treatments caused normochromic anemia and neutropenia.
Stability and Compatibility of Ceftazidime Administered by Continuous Infusion to Intensive Care Patients
Authors: Servais Hélène , Tulkens Paul M. 
Published: July 2002

ABSTRACT

The stability and compatibility of ceftazidime have been examined in the context of its potential use in concentrated solutions for continuous infusion in patients suffering from severe nosocomial pneumonia and receiving other intravenous medications by the same route. Ceftazidime stability in 4 to 12% solutions was found satisfactory (<10% degradation) for 24 h if kept at a temperature of 25°C (77°F) maximum. Studies mimicking the simultaneous administration of ceftazidime and other drugs as done in clinics showed physical incompatibilities with vancomycin, nicardipine, midazolam, and propofol and a chemical incompatibility with
N
-acetylcystein. Concentrated solutions (50 mg/ml) of erythromycin or clarithromycin caused the appearance of a precipitate, whereas gentamicin, tobramycin, amikacin, isepamicin, fluconazole, ketamine, sufentanil, valproic acid, furosemide, uradipil, and a standard amino acid solution were physically and chemically compatible.
Interaction of Common Azole Antifungals with P Glycoprotein
Authors: Wang Er-jia , Lew Karen , Casciano Christopher N. , Clement Robert P. , Johnson William W. 
Published: July 2002

ABSTRACT

Both eucaryotic and procaryotic cells are resistant to a large number of antibiotics because of the activities of export transporters. The most studied transporter in the mammalian ATP-binding cassette transporter superfamily, P glycoprotein (P-gp), ejects many structurally unrelated amphiphilic and lipophilic xenobiotics. Observed clinical interactions and some in vitro studies suggest that azole antifungals may interact with P-gp. Such an interaction could both affect the disposition and exposure to azole antifungal therapeutics and partially explain the clinical drug interactions observed with some antifungals. Using a whole-cell assay in which the retention of a marker substrate is evaluated and quantified, we studied the abilities of the most widely prescribed orally administered azole antifungals to inhibit the function of this transporter. In a cell line presenting an overexpressed amount of the human P-gp transporter, itraconazole and ketoconazole inhibited P-gp function with 50% inhibitory concentrations (IC
50
s) of ∼2 and ∼6 μM, respectively. Cyclosporin A was inhibitory with an IC
50
of 1.4 μM in this system. Uniquely, fluconazole had no effect in this assay, a result consistent with known clinical interactions. The effects of these azole antifungals on ATP consumption by P-gp (representing transport activity) were also assessed, and the
K

m

values were congruent with the IC
50
s. Therefore, exposure of tissue to the azole antifungals may be modulated by human P-gp, and the clinical interactions of azole antifungals with other drugs may be due, in part, to inhibition of P-gp transport.
Very Low Cefotaxime Concentrations Select for Hypermutable
Streptococcus pneumoniae
Populations
Authors: Negri María-Cristina , Morosini María-Isabel , Baquero María-Rosario , Campo Rosa del , Blázquez Jesús , Baquero Fernando 
Published: July 2002

ABSTRACT

A mixed culture of an hypermutable
hexA Streptococcus pneumoniae
mutant strain and its
hexA
+
isogenic ancestor was challenged with low cefotaxime concentrations. Despite identical original cefotaxime MICs, the
hexA
mutant population was significantly selected at very low concentrations, and all of the tested selected variants harbored the Thr550→Ala mutation in
pbp2x
. Since cefotaxime selects hypermutators, the risk of secondary acquisition of antibiotic resistance is increased; as expected, the cefotaxime-resistant mutants had a mutation frequency 10 times higher in response to to ciprofloxacin. The present study presents a model (not necessarily reflecting the clinical setting) illustrating the risk of selection of mutators in the evolution of multiple resistance.
In Vitro and In Vivo Activities of Gatifloxacin against
Mycobacterium tuberculosis
Authors: Alvirez-Freites Enrique J. , Carter Janna L. , Cynamon Michael H. 
Published: July 2002

ABSTRACT

Gatifloxacin (GAT) and moxifloxacin (MXF) were evaluated in vitro to determine their activities against
Mycobacterium tuberculosis
. GAT was subsequently compared in a dose range study to isoniazid (INH) in a murine tuberculosis model. GAT was somewhat less active than INH. GAT and MXF were evaluated in mice infected with
M. tuberculosis
and were found to have similar activities. GAT was studied alone and in combination with ethambutol, ethionamide (ETA), and pyrazinamide (PZA) and compared to INH and rifampin (RIF). GAT appears to have sufficient activity alone and in combination with ETA with or without PZA to merit evaluation for treatment of tuberculosis.
Malaria Parasites Giving Rise to Recrudescence In Vitro
Authors: Nakazawa Shusuke , Maoka Takashi , Uemura Haruki , Ito Yoshihiro , Kanbara Hiroji 
Published: July 2002

ABSTRACT
Recrudescences were simulated in vitro with drug treatment to examine how drug-sensitive parasites survive the treatment. Various numbers of cultured parasites were treated with lethal doses of pyrimethamine or mefloquine for various lengths of time. Recrudescences were observed in parasite populations with larger initial numbers of parasites when the treatment duration was prolonged. Equal numbers of parasitized erythrocytes were treated with various concentrations of pyrimethamine or mefloquine. There was no clear linear relationship between the incidence of recrudescence and the drug concentration. Parasites that had recrudesced were continuously allowed to recrudesce in the succeeding recrudescence experiments. Both the duration from the cessation of treatment to the time at which the recrudescent parasitemia level reached 1% and the growth rate of recrudescent parasites were equal among these recrudescences. The recrudescent parasites in these experiments were as sensitive to the drugs as the parasites tested before treatment were. These results suggest that a parasite culture may contain parasites in some phases that are not killed by drug for up to 10 days, which explains the recrudescences that occur even after treatment.
Double-Blind, Randomized, Placebo-Controlled Study of Topical 5% Acyclovir-1% Hydrocortisone Cream (ME-609) for Treatment of UV Radiation-Induced Herpes Labialis
Authors: Evans T. G. , Bernstein D. I. , Raborn G. W. , Harmenberg J. , Kowalski J. , Spruance S. L. 
Published: July 2002

ABSTRACT

Immunopathology is recognized as an important component of infectious disease manifestations, and corticosteroids have been used as an adjunct to antimicrobial therapy for a variety of conditions. Antiviral therapy of herpes labialis has been shown to result in only a small reduction in the time to healing and the duration of pain. To determine if topical application of a combination product containing 5% acyclovir and 1% hydrocortisone (ME-609) could provide benefit to herpes labialis patients, 380 immunocompetent adults with a history of herpes labialis were exposed to experimental UV radiation (UVR) to induce a recurrence. On day 2, just before the appearance of the majority of lesions (“delayed” lesions), subjects were randomized to receive active medication or vehicle control six times per day for 5 days. Overall, 120 of 380 patients developed delayed classical lesions, of whom 50 of 190 (26%) had been treated with ME-609 and 70 of 190 (37%) had received placebo (a reduction of 29% [
P
= 0.02]). Healing time, measured as the time to normal skin, was reduced by treatment with ME-609 (9.0 days for treated patients versus 10.1 days for the controls [
P
= 0.04]). There was a trend toward a reduction in the maximum lesion size in the ME-609 recipients compared to that in the controls (43 versus 60 mm
2
, respectively [
P
= 0.07]). The treatment had no effect on lesion pain, but ME-609 treatment reduced the number of patients with moderate or severe tenderness. Compared to treatment with a placebo, treatment with the combination antiviral-immunomodulatory cream provided benefit to patients with experimental UVR-induced herpes labialis, reducing classical lesion incidence, healing time, lesion size, and lesion tenderness. ME-609 is a novel product that merits further evaluation as a treatment for cold sores.
Cross-Resistance of Pink Bollworm (
Pectinophora gossypiella
) to
Bacillus thuringiensis
Toxins
Authors: Tabashnik Bruce E. , Liu Yong-Biao , de Maagd Ruud A. , Dennehy Timothy J. 
Published: July 2002

ABSTRACT

Two strains of pink bollworm (
Pectinophora gossypiella
) selected in the laboratory for resistance to
Bacillus thuringiensis
toxin Cry1Ac had substantial cross-resistance to Cry1Aa and Cry1Ab but not to Cry1Bb, Cry1Ca, Cry1Da, Cry1Ea, Cry1Ja, Cry2Aa, Cry9Ca, H04, or H205. The narrow spectrum of resistance and the cross-resistance to activated toxin Cry1Ab suggest that reduced binding of toxin to midgut target sites could be an important mechanism of resistance.
Characterization of pRGO1, a Plasmid from
Propionibacterium acidipropionici
, and Its Use for Development of a Host-Vector System in Propionibacteria
Authors: Kiatpapan Pornpimon , Hashimoto Yoshiteru , Nakamura Hisako , Piao Yong-Zhe , Ono Hisayo , Yamashita Mitsuo , Murooka Yoshikatsu 
Published: July 2002

ABSTRACT

The complete nucleotide sequence of pRGO1, a cryptic plasmid from
Propionibacterium acidipropionici
E214, was determined. pRGO1 is 6,868 bp long, and its G+C content is 65.0%. Frame analysis of the sequence revealed six open reading frames, which were designated Orf1 to Orf6. The deduced amino acid sequences of Orf1 and Orf2 showed extensive similarities to an initiator of plasmid replication, the Rep protein, of various plasmids of gram-positive bacteria. The amino acid sequence of the putative translation product of
orf3
exhibited a high degree of similarity to the amino acid sequences of DNA invertase in several bacteria. For the putative translation products of
orf4
,
orf5
, and
orf6
, on the other hand, no homologous sequences were found. The function of these open reading frames was studied by deletion analysis. A shuttle vector, pPK705, was constructed for shuttling between
Escherichia coli
and a
Propionibacterium
strain containing
orf1
(
repA
),
orf2
(
repB
),
orf5
, and
orf6
from pRGO1, pUC18, and the hygromycin B-resistant gene as a drug marker. Shuttle vector pPK705 successfully transformed
Propionibacterium freudenreichii
subsp.
shermanii
IFO12426 by electroporation at an efficiency of 8 × 10
6
CFU/μg of DNA under optimized conditions. Transformation of various species of propionibacteria with pPK705 was also performed at efficiencies of about 10
4
to 10
7
CFU/μg of DNA. The vector was stably maintained in strains of
P. freudenreichii
subsp.
shermanii
,
P. freudenreichii
,
P. pentosaceum
, and
P. freudenreichii
subsp.
freudenreichii
grown under nonselective conditions. Successful manipulation of a host-vector system in propionibacteria should facilitate genetic studies and lead to creation of genes that are useful industrially.
Denaturing Gradient Gel Electrophoresis Analysis of 16S Ribosomal DNA Amplicons To Monitor Changes in Fecal Bacterial Populations of Weaning Pigs after Introduction of
Lactobacillus reuteri
Strain MM53
Authors: Simpson Joyce M. , McCracken Vance J. , Gaskins H. Rex , Mackie Roderick I. 
Published: July 2002

ABSTRACT

The diversity and stability of the fecal bacterial microbiota in weaning pigs was studied after introduction of an exogenous
Lactobacillus reuteri
strain, MM53, using a combination of cultivation and techniques based on genes encoding 16S rRNA (16S rDNA). Piglets (
n
= 9) were assigned to three treatment groups (control, daily dosed, and 4th-day dosed), and fresh fecal samples were collected daily. Dosed animals received 2.5 × 10
10
CFU of antibiotic-resistant
L. reuteri
MM53 daily or every 4th day. Mean
Lactobacillus
counts for the three groups ranged from 1 × 10
9
to 4 × 10
9
CFU/g of feces. Enumeration of strain
L. reuteri
MM53 on MRS agar (Difco) plates containing streptomycin and rifampin showed that the introduced strain fluctuated between 8 × 10
3
and 5 × 10
6
CFU/g of feces in the two dosed groups. Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rDNA fragments, with primers specific for variable regions 1 and 3 (V1 and V3), was used to profile complexity of fecal bacterial populations. Analysis of DGGE banding profiles indicated that each individual maintained a unique fecal bacterial population that was stable over time, suggesting a strong host influence. In addition, individual DGGE patterns could be separated into distinct time-dependent clusters. Primers designed specifically to restrict DGGE analysis to a select group of lactobacilli allowed examination of interspecies relationships and abundance. Based on relative band migration distance and sequence determination,
L. reuteri
was distinguishable within the V1 region 16S rDNA gene patterns. Daily fluctuations in specific bands within these profiles were observed, which revealed an antagonistic relationship between
L. reuteri
MM53 (band V1-3) and another indigenous
Lactobacillus
assemblage (band V1-6).
Habituation of
Salmonella
spp. at Reduced Water Activity and Its Effect on Heat Tolerance
Authors: Mattick K. L. , Jørgensen F. , Legan J. D. , Lappin-Scott H. M. , Humphrey T. J. 
Published: July 2002

ABSTRACT

The effect of habituation at reduced water activity (a
w
) on heat tolerance of
Salmonella
spp. was investigated. Stationary-phase cells were exposed to a
w
0.95 in broths containing glucose-fructose, sodium chloride, or glycerol at 21°C for up to a week prior to heat challenge at 54°C. In addition, the effects of different a
w
s and heat challenge temperatures were investigated. Habituation at a
w
0.95 resulted in increased heat tolerance at 54°C with all solutes tested. The extent of the increase and the optimal habituation time depended on the solute used. Exposure to broths containing glucose-fructose (a
w
0.95) for 12 h resulted in maximal heat tolerance, with more than a fourfold increase in
D
54
values. Cells held for more than 72 h in these conditions, however, became as heat sensitive as nonhabituated populations. Habituation in the presence of sodium chloride or glycerol gave rise to less pronounced but still significant increases in heat tolerance at 54°C, and a shorter incubation time was required to maximize tolerance. The increase in heat tolerance following habituation in broths containing glucose-fructose (a
w
0.95) was RpoS independent. The presence of chloramphenicol or rifampin during habituation and inactivation did not affect the extent of heat tolerance achieved, suggesting that de novo protein synthesis was probably not necessary. These data highlight the importance of cell prehistory prior to heat inactivation and may have implications for food manufacturers using low-a
w
ingredients.