bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glycopeptide Susceptibility Profiles of
Staphylococcus haemolyticus
Bloodstream Isolates
Authors: Biavasco Francesca , Vignaroli Carla , Lazzarini Raffaella , Varaldo Pietro E. 
Published: July 2002

ABSTRACT

Twelve clinical strains of
Staphylococcus haemolyticus
(eight methicillin resistant and three methicillin susceptible), isolated from blood cultures between 1982 and 1997, were investigated for teicoplanin and vancomycin susceptibility profiles. On the basis of conventional MIC tests and breakpoints, four isolates were susceptible (MICs, 1 to 8 μg/ml) and eight were resistant (MICs, 32 to 64 μg/ml) to teicoplanin while all were susceptible to vancomycin (MICs, 1 to 2 μg/ml). All four strains for which the conventional teicoplanin MICs were within the range of susceptibility expressed heterogeneous resistance to teicoplanin and homogeneous vancomycin susceptibility. Of the eight strains for which the conventional teicoplanin MICs were within the range of resistance, six expressed heterogeneous and two expressed homogeneous teicoplanin resistance while seven showed heterogeneous vancomycin resistance profiles (with subpopulations growing on 8 μg of the drug per ml at frequencies of ≥10
−6
for six strains and 10
−7
for one) and one demonstrated homogeneous vancomycin susceptibility. Of six bloodstream isolates of other staphylococcal species (
S. aureus
,
S. epidermidis
, and
S. simulans
), for all of which the conventional teicoplanin MICs were ≥4 μg/ml and the vancomycin MICs were ≤2 μg/ml, none exhibited heterogeneous susceptibility profiles for teicoplanin while three showed homogeneous and three showed heterogeneous susceptibility profiles for vancomycin (with subpopulations growing on 8 μg of the drug per ml found for only one strain). The results of this study indicate that a heterogeneous response to glycopeptides is a common feature of
S. haemolyticus
isolates and suggest that susceptibility to glycopeptides as determined by conventional MIC tests may not be predictive of the outcome of glycopeptide therapy.
Genetic Characterization of
vanG
, a Novel Vancomycin Resistance Locus of
Enterococcus faecalis
Authors: McKessar Stuart J. , Berry Anne M. , Bell Jan M. , Turnidge John D. , Paton James C. 
Published: July 2002

ABSTRACT

Enterococcus faecalis
strain WCH9 displays a moderate level of resistance to vancomycin (MIC = 16 μg/ml) and full susceptibility to teicoplanin but is negative by PCR analysis using primers specific for all known enterococcal vancomycin resistance genotypes (
vanA
,
vanB
,
vanC
,
vanD
, and
vanE
). We have isolated and sequenced a novel putative vancomycin resistance locus (designated
vanG
), which contains seven open reading frames, from this strain. These are organized differently from those of all the other enterococcal
van
loci, and, furthermore, the individual
vanG
gene products exhibit less than 50% amino acid sequence identity to other
van
gene products.
Development of Resistance to Ciprofloxacin, Rifampin, and Mupirocin in Methicillin-Susceptible and -Resistant
Staphylococcus aureus
Isolates
Authors: Schmitz Franz-Josef , Fluit Ad C. , Hafner Dieter , Beeck Andreas , Perdikouli Mirella , Boos Mechthild , Scheuring Sybille , Verhoef Jan , Köhrer Karl , Von Eiff Christof 
Published: July 2002

ABSTRACT

A relationship between resistance to methicillin and resistance to fluoroquinolones, rifampin, and mupirocin has been described for
Staphylococcus aureus
. Differences in resistance rates may be explainable by a higher spontaneous mutation rate (MR) or a faster development of resistance (DIFF) in methicillin-resistant
S. aureus
(MRSA). No differences in MR, DIFF, and mutations in
grlA
and
gyrA
were detected between methicillin-susceptible
S. aureus
and MRSA. The higher resistance rates in MRSA are not the result of hypermutability of target genes or a faster emergence of different mutations and may be the consequence of clonal spread of multiresistant MRSA.
Variation within the
vat
(E) Allele of
Enterococcus faecium
Isolates from Retail Poultry Samples
Authors: Simjee S. , McDermott P. F. , Wagner D. D. , White D. G. 
Published: July 2002

ABSTRACT

In a survey of retail meat samples, twelve quinupristin-dalfopristin-resistant (MICs, ≥4 mg/liter)
Enterococcus faecium
isolates that carried a
vat
(E) gene were recovered. DNA sequence comparison revealed five new variations in the
vat
(E) allele among 12 isolates, which were designated
vat
(E-4) through
vat
(E-8); two isolates had
vat
(E-1). There was no correlation between the number of base changes and the quinupristin-dalfopristin MIC.
Activities of New Macrolides and Fluoroquinolones against
Mycobacterium ulcerans
Infection in Mice
Authors: Bentoucha Abdelhalim , Robert Jérôme , Dega Hervé , Lounis Nacer , Jarlier Vincent , Grosset Jacques 
Published: July 2002

ABSTRACT

Mice infected in the left hind footpad with 5 log
10
acid-fast bacilli of
Mycobacterium ulcerans
were divided into an untreated control group and 17 treatment groups that received one of the following regimens for 4 weeks (all doses in milligrams per kilogram): 100 mg of azithromycin (AZM), 100 mg of clarithromycin (CLR), or 50 mg of AZM for a duration of 5 days a week (daily), three times a week, or once weekly. In addition, the following regimens were administered daily: 100 mg of telithromycin (TLM), sparfloxacin (SPX), or moxifloxacin (MOX); 200 mg of levofloxacin (LVX); 100 mg of streptomycin (STR) or amikacin (AMK); 10 mg of rifampin (RIF); and the combination of 10 mg of RIF and 100 mg of AMK (RIF+AMK). After completion of treatment, mice were observed for 30 weeks. The effectiveness of treatment regimens was assessed in terms of the delay in median time to footpad swelling in treated mice compared with that in the untreated controls. Clear-cut bactericidal activity, i.e., an observed delay in footpad swelling that exceeded the period of treatment, was observed in the STR-, AMK-, and RIF+AMK-treated mice. However, all mice treated with either AMK or STR alone had swollen footpads before the end of the 30-week observation period, suggesting regrowth of
M. ulcerans
. In contrast, 50% of the mice treated with the RIF+AMK combination exhibited no lesion even after 30 weeks, suggesting cure. The remaining regimens could be assigned to one of three groups: (i) no activity (50 mg of AZM, 100 mg of AZM thrice weekly, TLM, and LVX); (ii) bacteriostatic activity, i.e., a delay in footpad swelling shorter than the 4-week treatment duration (100 mg of AZM daily or once weekly, CLR thrice or once weekly, and MOX); or (iii) weak bactericidal activity (CLR daily and SPX). The RIF+AMK combination and possibly RIF+STR warrant further study for the treatment
of M. ulcerans
infection in humans.
Susceptibilities of Oral Bacteria and Yeast to Mammalian Cathelicidins
Authors: Guthmiller Janet M. , Vargas Kaaren G. , Srikantha Rupasree , Schomberg Lori L. , Weistroffer Paula L. , McCray Paul B. , Tack Brian F. 
Published: July 2002

ABSTRACT

The effects of cathelicidins against oral bacteria and clinically important oral yeasts are not known. We tested the susceptibilities of
Actinobacillus actinomycetemcomitans
,
Fusobacterium nucleatum
,
Porphyromonas gingivalis
,
Streptococcus sanguis
,
Candida krusei
,
Candida tropicalis
and
Candida albicans
to the following cathelicidins: FALL39, SMAP29, and CAP18. SMAP29 and CAP18 were antimicrobial, whereas FALL39 did not exhibit antimicrobial activity. Future studies are needed to determine the potential use of these antimicrobial peptides in prevention and treatment of oral infections.
Quantitative PCR Assay To Measure
Aspergillus fumigatus
Burden in a Murine Model of Disseminated Aspergillosis: Demonstration of Efficacy of Caspofungin Acetate
Authors: Bowman J. C. , Abruzzo G. K. , Anderson J. W. , Flattery A. M. , Gill C. J. , Pikounis V. B. , Schmatz D. M. , Liberator P. A. , Douglas C. M. 
Published: July 2002

ABSTRACT

Caspofungin acetate (MK-0991) is an antifungal antibiotic that inhibits the synthesis of 1,3-β-
d
-glucan, an essential component of the cell wall of several pathogenic fungi. Caspofungin acetate was recently approved for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies. The activity of 1,3-β-
d
-glucan synthesis inhibitors against
Aspergillus fumigatus
has been evaluated in animal models of pulmonary or disseminated disease by using prolongation of survival or reduction in tissue CFU as assay endpoints. Because these methods suffer from limited sensitivity or poor correlation with fungal growth, we have developed a quantitative PCR-based (qPCR) (TaqMan) assay to monitor disease progression and measure drug efficacy.
A. fumigatus
added to naı̈ve, uninfected kidneys as either ungerminated conidia or small germlings yielded a linear qPCR response over at least 4 orders of magnitude. In a murine model of disseminated aspergillosis, a burden of
A. fumigatus
was detected in each of five different organs at 4 days postinfection by the qPCR assay, and the mean fungal load in these organs was 1.2 to 3.5 log
10
units greater than mean values determined by CFU measurement. When used to monitor disease progression in infected mice, the qPCR assay detected an increase of nearly 4 log
10
conidial equivalents/g of kidney between days 1 and 4 following infection, with a peak fungal burden that coincided with the onset of significant mortality. Traditional CFU methodology detected only a marginal increase in fungal load in the same tissues. In contrast, when mice were infected with
Candida albicans
, which does not form true mycelia in tissues, quantitation of kidney burden by both qPCR and CFU assays was strongly correlated as the infection progressed. Finally, treatment of mice with induced disseminated aspergillosis with either caspofungin or amphotericin B reduced the
A. fumigatus
burden in infected kidneys to the limit of detection for the qPCR assay. Because of its much larger dynamic range, the qPCR assay is superior to traditional CFU determination for monitoring the progression of disseminated aspergillosis and evaluating the activity of antifungal antibiotics against
A. fumigatus
.
Bactericidal Activities of Two Daptomycin Regimens against Clinical Strains of Glycopeptide Intermediate-Resistant
Staphylococcus aureus
, Vancomycin-Resistant
Enterococcus faecium
, and Methicillin-Resistant
Staphylococcus aureus
Isolates in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations
Authors: Akins Ronda L. , Rybak Michael J. 
Published: July 2002

ABSTRACT

Daptomycin is an investigational lipopeptide antibiotic active against gram-positive organisms. The mechanism of action is unique, resulting in interference with cell membrane transport. The bactericidal activity of daptomycin was evaluated against glycopeptide-intermediate susceptible
Staphylococcus aureus
(GISA), vancomycin-resistant
Enterococcus faecium
(VREF), and methicillin-resistant
S. aureus
(MRSA) in an in vitro infection model with simulated endocardial vegetations. Simulated regimens of daptomycin at 6 mg/kg/day (D6) and 10 mg/kg/day (D10) were utilized. MICs and MBCs for daptomycin were determined in the absence and in the presence of albumin with the following results (MIC/MBC): for GISA-992, 0.5/1.0 and 16/16; for VREF-590, 2.0/2.0 and 32/32; and for MRSA-494, 0.25/0.25 and 1.0/4.0 μg/ml, respectively. During the first 8 h daptomycin significantly reduced the inoculum for all organisms. Daptomycin at 6 mg/kg/day and 10 mg/kg/day had log
10
CFU/g reductions of 5 and 6, 3.4 and 5, and 6.4 and 6.5 by 8 h for GISA-992, VREF-590, and MRSA-494, respectively. Against both GISA-992 and VREF-590, the D10 regimen achieved the limit of detection at 72 h, with D6 regimens showing slight regrowth. A concentration-dependent killing effect was noted to occur, with daptomycin demonstrating a more rapid and greater kill from the D10 versus the D6 regimen. The results of this study suggest that daptomycin demonstrates significant (
P
< 0.05) activity against gram-positive organisms in a simulated sequestered infection site.
Synergy of Histone-Derived Peptides of Coho Salmon with Lysozyme and Flounder Pleurocidin
Authors: Patrzykat Aleksander , Zhang Lijuan , Mendoza Valentina , Iwama George K. , Hancock Robert E. W. 
Published: July 2002

ABSTRACT

Recent research has identified endogenous cationic antimicrobial peptides as important factors in the innate immunity of many organisms, including fish. It is known that antimicrobial activity, as well as lysozyme activity, can be induced in coho salmon (
Oncorhynchus kisutch
) mucus after exposure of the fish to infectious agents. Since lysozyme alone does not have antimicrobial activity against
Vibrio anguillarum
and
Aeromonas salmonicida
, a four-step protein purification protocol was used to isolate and identify antibacterial fractions from bacterially challenged coho salmon mucus and blood. The purification consisted of extraction with hot acetic acid, extraction and concentration on a C
18
cartridge, gel filtration, and reverse-phase chromatography on a C
18
column. N-terminal amino acid sequence analyses revealed that both the blood and the mucus antimicrobial fractions demonstrated identity with the N terminus of trout H1 histone. Mass spectroscopic analysis indicated the presence of the entire histone, as well as fragments thereof, including a 26-amino-acid N-terminal segment. These fractions inhibited the growth of antibiotic-supersuscptible
Salmonella enterica
serovar Typhimurium, as well as
A. salmonicida
and
V. anguillarum
. Synthetic peptides identical to the N-terminally acetylated or C-terminally amidated 26-amino-acid fragment were inactive in antimicrobial assays, but they potentiated the antimicrobial activities of the flounder peptide pleurocidin, lysozyme, and crude lysozyme-containing extracts from coho salmon. The peptides bound specifically to anionic lipid monolayers. However, synergy with pleurocidin did not appear to occur at the cell membrane level. The synergistic activities of inducible histone peptides indicate that they play an important role in the first line of salmon defenses against infectious pathogens and that while some histone fragments may have direct antimicrobial effects, others improve existing defenses.
Antimonial-Mediated DNA Fragmentation inLeishmania infantumAmastigotes
Authors: Sereno Denis , Holzmuller Philippe , Mangot Isabelle , Cuny Gérard , Ouaissi Ali , Lemesre Jean-Loup 
Published: July 2002

ABSTRACTThe basic treatment of leishmaniasis consists in the administration of pentavalent antimonials. The mechanisms that contribute to pentavalent antimonial toxicity against the intracellular stage of the parasite (i.e., amastigote) are still unknown. In this study, the combined use of several techniques including DNA fragmentation assay and in situ and cytofluorometry terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling methods and YOPRO-1 staining allowed us to demonstrate that potassium antimonyl tartrate, an Sb(III)-containing drug, was able to induce cell death associated with DNA fragmentation in axenic amastigotes ofLeishmania infantumat low concentrations (10 μg/ml). This observation was in close correlation with the toxicity of Sb(III) species against axenic amastigotes (50% inhibitory concentration of 4.75 μg/ml). Despite some similarities to apoptosis, nuclease activation was not a consequence of caspase-1, caspase-3, calpain, cysteine protease, or proteasome activation. Altogether, our results demonstrate that the antileishmanial toxicity of Sb(III) antimonials is associated with parasite oligonucleosomal DNA fragmentation, indicative of the occurrence of late events in the overall process of apoptosis. The elucidation of the biochemical pathways leading to cell death could allow the isolation of new therapeutic targets.
Echinococcus multilocularis
Alkaline Phosphatase as a Marker for Metacestode Damage Induced by In Vitro Drug Treatment with Albendazole Sulfoxide and Albendazole Sulfone
Authors: Stettler Marianne , Siles-Lucas Mar , Sarciron Elisabeth , Lawton Philippe , Gottstein Bruno , Hemphill Andrew 
Published: July 2002

ABSTRACT

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm
Echinococcus multilocularis
. The disease affects the human liver and occasionally other organs and is fatal if treatment is unsuccessful. The present chemotherapy of AE is based on the administration of benzimidazole carbamate derivatives, such as mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some cases, parasitostatic rather than parasiticidal, and the recurrence rate is rather high. Therefore, chemotherapy usually involves the lifelong uptake of massive doses of albendazole and new treatment options are urgently needed. In order to avoid costly and time-consuming animal experimentation, a first step in searching for novel parasiticidal compounds could be the in vitro drug screening of novel compounds by employing metacestode cultivation. However, presently used techniques (e.g., transmission electron microscopy) for determination of parasite viability involve costly equipment and time-consuming preparation of rather large amounts of parasite material. We therefore searched for a parasite marker which can be easily traced and the presence or absence of which is indicative of parasite viability. In this study we show that the increase of
E. multilocularis
alkaline phosphatase activity in culture supernatants during in vitro drug treatment with albendazole derivatives correlates with the progressive degeneration and destruction of the metacestode tissue. The inexpensive and rapid assay presented here will serve as an ideal tool for performing first-round in vitro tests on the efficacy of a large number of antiparasitic compounds.
Risk Factors for Emergence of Resistance to Broad-Spectrum Cephalosporins among
Enterobacter
spp
Authors: Kaye Keith S. , Cosgrove Sara , Harris Anthony , Eliopoulos George M. , Carmeli Yehuda 
Published: July 2002

ABSTRACT

Among 477 patients with susceptible
Enterobacter
spp., 49 subsequently harbored third-generation cephalosporin-resistant
Enterobacter
spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3,
P
= 0.01); quinolone therapy was protective (OR = 0.4,
P
= 0.03). There were trends toward decreased risk for resistance among patients receiving broad-spectrum cephalosporins and either aminoglycosides or imipenem. Of the patients receiving broad-spectrum cephalosporins, 19% developed resistance.
Bacilysocin, a Novel Phospholipid Antibiotic Produced by
Bacillus subtilis
168
Authors: Tamehiro Norimasa , Okamoto-Hosoya Yoshiko , Okamoto Susumu , Ubukata Makoto , Hamada Masa , Naganawa Hiroshi , Ochi Kozo 
Published: July 2002

ABSTRACT

We have found a novel phospholipid antibiotic (named bacilysocin) which accumulates within (or associates with) the cells of
Bacillus subtilis
168 and determined the structure by nuclear magnetic resonance and mass spectrometry analyses. The structure of bacilysocin elucidated was 1-(12-methyltetradecanoyl)-3-phosphoglyceroglycerol. Bacilysocin demonstrated antimicrobial activity, especially against certain fungi. Production of bacilysocin commenced immediately after growth ceased and before the formation of heat-resistant spores. The production of bacilysocin was completely blocked when the
ytpA
gene, which encodes a protein homologous to lysophospholipase, was disrupted, but blockage of the
ytpA
gene did not significantly affect growth. Sporulation was also impaired, with a 10-fold reduction in heat-resistant spore titers being detected. Since the
ytpA
disruptant actually lacked phospholipase activity, we propose that the YtpA protein functions as an enzyme for the biosynthesis of bacilysocin.
Gemifloxacin Is Efficacious against Penicillin-Resistant and Quinolone-Resistant Pneumococci in Experimental Meningitis
Authors: Cottagnoud Philippe , Acosta Fernando , Cottagnoud Marianne , Täuber Martin G. 
Published: July 2002

ABSTRACT

In experimental rabbit meningitis, gemifloxacin penetrated inflamed meninges well (22 to 33%) and produced excellent bactericidal activity (change in log
10
[Δlog
10
] CFU/ml/h, −0.68 ± 0.30 [mean and standard deviation]), even superior to that of the standard regimen of ceftriaxone plus vancomycin (−0.49 ± 0.09 Δlog
10
CFU/ml/h), in the treatment of meningitis due to a penicillin-resistant pneumococcal strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, gemifloxacin showed good bactericidal activity (−0.48 ± 0.16 Δlog
10
CFU/ml/h). The excellent antibacterial activity of gemifloxacin was also confirmed by time-kill assays over 8 h in vitro.
Cytochrome
c
3
Mutants of
Desulfovibrio desulfuricans
Authors: Rapp-Giles Barbara J. , Casalot Laurence , English R. Samuel , Ringbauer Joseph A. , Dolla Alain , Wall Judy D. 
Published: July 2002

ABSTRACT

To explore the physiological role of tetraheme cytochrome
c
3
in the sulfate-reducing bacterium
Desulfovibrio desulfuricans
G20, the gene encoding the preapoprotein was cloned, sequenced, and mutated by plasmid insertion. The physical analysis of the DNA from the strain carrying the integrated plasmid showed that the insertion was successful. The growth rate of the mutant on lactate with sulfate was comparable to that of the wild type; however, mutant cultures did not achieve the same cell densities. Pyruvate, the oxidation product of lactate, served as a poor electron source for the mutant. Unexpectedly, the mutant was able to grow on hydrogen-sulfate medium. These data support a role for tetraheme cytochrome
c
3
in the electron transport pathway from pyruvate to sulfate or sulfite in
D. desulfuricans
G20.
Flow Cytometry for Determination of the Efficacy of Contact Lens Disinfecting Solutions against
Acanthamoeba
spp
Authors: Borazjani Roya N. , May Lauren L. , Noble Judith A. , Avery Simon V. , Ahearn Donald G. 
Published: July 2002

ABSTRACT

Flow cytometric analyses of cellular staining with fluorescent viability dyes and direct microscopic observations of methylene blue exclusion were compared for evaluation of the effects of a chlorhexidine gluconate-based contact lens disinfectant solution and a polyhexamethylene biguanide solution against cysts and trophozoites of
Acanthamoeba castellanii
and
Acanthamoeba polyphaga
. The flow cytometric procedure with propidium iodide (used to stain dead cells) indicated that more than 90% of trophozoites of both species (inocula of 10
5
to 10
6
/ml) at 22°C lost their viability after 4 h of exposure to chlorhexidine. When propidium iodide was used in combination with fluorescein diacetate (for live cells), the apparent number of propidium iodide-stained cells was reduced, but the relative efficacies of the two biguanide solutions appeared unchanged from those evident with the single dyes; the chlorhexidine solution was more effective than the polyhexamethylene biguanide solution. Similar data were obtained with the more cumbersome methylene blue exclusion procedure. Flow cytometric analyses provided a statistically reproducible and rapid procedure for determining the relative antiamoebal efficacies of the disinfecting solutions.