bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States
Authors: Jones Mark E. , Staples Angela M. , Critchley Ian , Thornsberry Clyde , Heinze Paul , Engler Howard D. , Sahm Daniel F. 
Published: July 2002

ABSTRACT

To benchmark the activity of moxifloxacin (a newer fluoroquinolone), a U.S. study comprising 16,141 contemporary isolates of
Streptococcus pneumoniae
(5,640),
Haemophilus influenzae
(6,583), and
Moraxella catarrhalis
(3,648) referred from 377 institutions during 1998 is described. For
S. pneumoniae
the modal MIC and MIC at which 90% of the isolates were inhibited (MIC
90
) for moxifloxacin were 0.12 and 0.25 μg/ml, respectively, independent of susceptibility to other drug classes, geography, or site of infection. Eleven isolates were intermediate or resistant to levofloxacin and grepafloxacin; of these isolates, 1 remained susceptible to sparfloxacin, 2 remained susceptible to moxifloxacin, and 4 remained susceptible to trovafloxacin. All 11 isolates possessed classic mutations in
gyrA
and/or
parC
known to confer reduced susceptibility to fluoroquinolones. Four isolates (originating from four separate states) belonging to a multidrug-resistant, fluoroquinolone-resistant clone were identified by pulsed-field gel electrophoresis. For moxifloxacin and trovafloxacin, at least 87% of isolates demonstrated MICs ≥3 twofold concentrations below the susceptibility breakpoints, in contrast to no more than 15% for levofloxacin, grepafloxacin, and sparfloxacin. Of the isolates that were multidrug resistant (7.4%), >98% remained susceptible to moxifloxacin. The modal MIC and MIC
90
for
M. catarrhalis
(both 0.06 μg/ml) and for
H. influenzae
(both 0.03 μg/ml) were independent of β-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future studies.
Structural and Topological Differences between a Glycopeptide-Intermediate Clinical Strain and Glycopeptide-Susceptible Strains of
Staphylococcus aureus
Revealed by Atomic Force Microscopy
Authors: Boyle-Vavra Susan , Hahm Jongin , Sibener S. J. , Daum Robert S. 
Published: July 2002

ABSTRACT

Novel cell surface topography was revealed on cocci from a glycopeptide-intermediate
Staphylococcus aureus
(GISA) clinical strain by using atomic force microscopy. The GISA isolate and its revertant had two parallel circumferential surface rings. One equatorial surface ring was observed in control strains. In vancomycin-susceptible strains, additional rings were formed in the presence of vancomycin. Ring depth measurements also revealed striking differences between the GISA strain and susceptible strains grown with or without vancomycin.
Use of Molecular Beacons To Detect an Antifolate Resistance-Associated Mutation in
Plasmodium falciparum
Authors: Durand Rémy , Eslahpazire Jobin , Jafari Sayeh , Delabre Jean-François , Marmorat-Khuong Anne , di Piazza Jean-Philippe , Le Bras Jacques 
Published: July 2002

ABSTRACT

A PCR-based technique using new fluorescent probes, called molecular beacons, was developed to detect the antifolate resistance-associated S108N point mutation in
Plasmodium falciparum
. One hundred African clinical isolates were tested by the new method in comparison with the PCR-restriction fragment length polymorphism method. This new molecular technique appears to be a promising tool for epidemiological studies.
Quinupristin-Dalfopristin Combined with β-Lactams for Treatment of Experimental Endocarditis Due to
Staphylococcus aureus
Constitutively Resistant to Macrolide-Lincosamide-Streptogramin B Antibiotics
Authors: Vouillamoz J. , Entenza J. M. , Féger C. , Glauser M. P. , Moreillon P. 
Published: July 2002

ABSTRACT

Quinupristin-dalfopristin (Q-D) is an injectable streptogramin active against most gram-positive pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA). In experimental endocarditis, however, Q-D was less efficacious against MRSA isolates constitutively resistant to macrolide-lincosamide-streptogram B (C-MLS
B
) than against MLS
B
-susceptible isolates. To circumvent this problem, we used the checkerboard method to screen drug combinations that would increase the efficacy of Q-D against such bacteria. β-Lactams consistently exhibited additive or synergistic activity with Q-D. Glycopeptides, quinolones, and aminoglycosides were indifferent. No drugs were antagonistic. The positive Q-D–β-lactam interaction was independent of MLS
B
or β-lactam resistance. Moreover, addition of Q-D at one-fourth the MIC to flucloxacillin-containing plates decreased the flucloxacillin MIC for MRSA from 500 to 1,000 mg/liter to 30 to 60 mg/liter. Yet, Q-D–β-lactam combinations were not synergistic in bactericidal tests. Rats with aortic vegetations were infected with two C-MLS
B
-resistant MRSA isolates (isolates AW7 and P8) and were treated for 3 or 5 days with drug dosages simulating the following treatments in humans: (i) Q-D at 7 mg/kg two times a day (b.i.d.) (a relatively low dosage purposely used to help detect positive drug interactions), (ii) cefamandole at constant levels in serum of 30 mg/liter, (iii) cefepime at 2 g b.i.d., (iv) Q-D combined with either cefamandole or cefepime. Any of the drugs used alone resulted in treatment failure. In contrast, Q-D plus either cefamandole or cefepime significantly decreased valve infection compared to the levels of infection for both untreated controls and those that received monotherapy (
P
< 0.05). Importantly, Q-D prevented the growth of highly β-lactam-resistant MRSA in vivo. The mechanism of this beneficial drug interaction is unknown. However, Q-D–β-lactam combinations might be useful for the treatment of complicated infections caused by multiple organisms, including MRSA.
β-Lactamases in
Shigella flexneri
Isolates from Hong Kong and Shanghai and a Novel OXA-1-Like β-Lactamase, OXA-30
Authors: Siu L. K. , Lo J. Y. C. , Yuen K. Y. , Chau P. Y. , Ng M. H. , Ho P. L. 
Published: July 2002

ABSTRACT

Ninety-one ampicillin-resistant
Shigella flexneri
strains from Hong Kong and Shanghai were studied for production of β-lactamases. TEM-1-like and OXA-1-like enzymes were identified in 21 and 79% of the strains, respectively, by isoelectric focusing (IEF). No difference in the pattern of β-lactamase production was found between strains from Hong Kong and Shanghai. Four ribotypes were detected. Over 88% of OXA-producing strains had the same ribotype. All TEM-1-like strains harbored a plasmid which hybridized positively with the
bla
TEM
probe. Total DNA from OXA-1-like strains failed to hybridize or only hybridized weakly with an OXA probe. The OXA resistance was not transferable. OXA-1-like enzymes exhibited substrate and inhibition profiles similar to that of OXA-1 and were shown to have a pI of 7.3 by further IEF using a narrow-range ampholine gel. The gene encoding the OXA-1-like enzyme from one isolate (CH-07) was cloned, sequenced, and found to differ from
bla
OXA-1
at codon 131 (AGA→GGA; Arg to Gly), resulting in the novel designation OXA-30. The predominance of OXA-type enzymes in ampicillin-resistant
S. flexneri
suggests host preference for specific β-lactamases.
Relationships of the Area under the Curve/MIC Ratio to Different Integral Endpoints of the Antimicrobial Effect: Gemifloxacin Pharmacodynamics in an In Vitro Dynamic Model
Authors: Firsov Alexander A. , Lubenko Irene Y. , Portnoy Yury A. , Zinner Stephen H. , Vostrov Sergey N. 
Published: July 2002

ABSTRACT

Most integral endpoints of the antimicrobial effect are determined over an arbitrarily chosen time period, such as the dosing interval (τ), regardless of the actual effect duration. Unlike the τ-related endpoints, the intensity of the antimicrobial effect (
I
E
) does consider its duration—from time zero to the time when bacterial counts on the regrowth curve achieve the same maximal numbers as in the absence of the antimicrobial. To examine the possible impact of this fundamental difference on the relationships of the antimicrobial effect to the ratio of the area under the concentration-time curve (AUC) to the MIC, a clinical isolate of
Staphylococcus aureus
was exposed to simulated gemifloxacin pharmacokinetics over a 40-fold range of AUC/MIC ratios, from 11 to 466 h. In each run,
I
E
and four τ-related endpoints, including the area under the time-kill curve (AUBC), the area above the curve (AAC), the area between the control growth and time-kill curves (ABBC), and the ABBC related to the area under the control growth curve (AUGC), were calculated for τ = 24 h. Unlike the
I
E
, which displayed pseudolinear relationships with the AUC/MIC ratio; each τ-related endpoint showed a distinct saturation at potentially therapeutic AUC/MIC ratios (116 to 466 h) when the antimicrobial effect persisted longer than τ. This saturation results from the underestimation of the true effect and may be eliminated if ABBC, AAC, and AUBC (but not AUGC) are modified and determined in the same manner as the
I
E
to consider the actual effect duration. These data suggest a marginal value of the τ-related endpoints as indices of the total antimicrobial effect. Since all of them respond to AUC/MIC ratio changes less than the
I
E
, the latter is preferable in comparative pharmacodynamic studies.
Antimicrobial Susceptibilities of Unique
Stenotrophomonas maltophilia
Clinical Strains
Authors: Valdezate Sylvia , Vindel Ana , Loza Elena , Baquero Fernando , Cantón Rafael 
Published: July 2002

ABSTRACT

Susceptibility to 41 antimicrobials was studied with 99
Stenotrophomonas maltophilia
strains, and different pulsed-field gel electrophoresis profiles were identified among 130 prospectively collected isolates. Moxalactam, doxycycline, minocycline, and clinafloxacin displayed the highest activity (≥98% susceptibility). Ticarcillin resistance (75%) was reverted by clavulanate in 25% of strains. Trimethoprim-sulfamethoxazole resistance was 26.2% (≥4 [trimethoprim]/76 [sulfamethoxazole] μg/ml) and dropped to 11.1% when an 8/152-μg/ml breakpoint was applied based on its bimodal MIC distribution. Resistance was lower when unique strains were considered, because clonal organisms contribute to resistance.
Activation of Multiple Antibiotic Resistance in Uropathogenic
Escherichia coli
Strains by Aryloxoalcanoic Acid Compounds
Authors: Balagué Claudia , Véscovi Eleonora Garcı́a 
Published: July 2002

ABSTRACT

Clofibric and ethacrynic acids are prototypical pharmacological agents administered in the treatment of hypertrigliceridemia and as a diuretic agent, respectively. They share with 2,4-dichlorophenoxyacetic acid (the widely used herbicide known as 2,4-D) a chlorinated phenoxy structural moiety. These aryloxoalcanoic agents (AOAs) are mainly excreted by the renal route as unaltered or conjugated active compounds. The relatedness of these agents at the structural level and their potential effect on therapeutically treated or occupationally exposed individuals who are simultaneously undergoing a bacterial urinary tract infection led us to analyze their action on uropathogenic, clinically isolated
Escherichia coli
strains. We found that exposure to these compounds increases the bacterial resistance to an ample variety of antibiotics in clinical isolates of both uropathogenic and nonpathogenic
E. coli
strains. We demonstrate that the AOAs induce an alteration of the bacterial outer membrane permeability properties by the repression of the major porin OmpF in a
micF
-dependent process. Furthermore, we establish that the antibiotic resistance phenotype is primarily due to the induction of the MarRAB regulatory system by the AOAs, while other regulatory pathways that also converge into
micF
modulation (OmpR/EnvZ, SoxRS, and Lrp) remained unaltered. The fact that AOAs give rise to uropathogenic strains with a diminished susceptibility to antimicrobials highlights the impact of frequently underestimated or ignored collateral effects of chemical agents.
Susceptibilities of
Mycoplasma hominis, M. pneumoniae
, and
Ureaplasma urealyticum
to GAR-936, Dalfopristin, Dirithromycin, Evernimicin, Gatifloxacin, Linezolid, Moxifloxacin, Quinupristin-Dalfopristin, and Telithromycin Compared to Their Susceptibilities to Reference Macrolides, Tetracyclines, and Quinolones
Authors: Kenny George E. , Cartwright Frank D. 
Published: July 2002

ABSTRACT

The susceptibilities of
Mycoplasma hominis
,
Mycoplasma pneumoniae
, and
Ureaplasma urealyticum
to eight new antimicrobial agents were determined by agar dilution.
M. pneumoniae
was susceptible to the new glycylcycline GAR-936 at 0.12 μg/ml and evernimicin at 4 μg/ml, but it was resistant to linezolid. It was most susceptible to dirithromycin, quinupristin-dalfopristin, telithromycin, reference macrolides, and josamycin.
M. hominis
was susceptible to linezolid, evernimicin, and GAR-936. It was resistant to macrolides and the ketolide telithromycin but susceptible to quinupristin-dalfopristin and josamycin.
U. urealyticum
was susceptible to evernimicin (8 to 16 μg/ml) and resistant to linezolid. It was less susceptible to GAR-936 (4.0 μg/ml) than to tetracycline (0.5 μg/ml). Telithromycin and quinupristin-dalfopristin were the most active agents against ureaplasmas (0.06 μg/ml). The new quinolone gatifloxacin was active against
M. pneumoniae
and
M. hominis
at 0.12 to 0.25 μg/ml and active against ureaplasmas at 1.0 μg/ml. The MICs of macrolides were markedly affected by pH, with an 8- to 32-fold increase in the susceptibility of
M. pneumoniae
as the pH increased from 6.9 to 7.8. A similar increase in susceptibility with increasing pH was also observed with ureaplasmas. Tetracyclines showed a fourfold increase of activity as the pH decreased 1 U, whereas GAR-936 showed a fourfold decrease in activity with a decrease in pH.
DNA Sequence Analysis of
rdxA
and
frxA
from 12 Pairs of Metronidazole-Sensitive and -Resistant Clinical
Helicobacter pylori
Isolates
Authors: Kwon D. H. , Hulten K. , Kato M. , Kim J. J. , Lee M. , El-Zaatari F. A. K. , Osato M. S. , Graham D. Y. 
Published: July 2002

ABSTRACT

We previously reported that inactivation of
rdxA
and/or
frxA
converted
Helicobacter pylori
from metronidazole sensitive to metronidazole resistant. To examine the individual roles of
rdxA
and
frxA
in the development of metronidazole resistance in
H. pylori
, we examined the status of
rdxA
and
frxA
from 12 pairs of metronidazole-sensitive and -resistant
H. pylori
isolates obtained following unsuccessful therapy containing metronidazole. Arbitrary primed fingerprinting analyses revealed that the genotypes of 11 sensitive and resistant pairs of strains were essentially identical. Amino acid sequence identities of RdxA and FrxA from the 14 metronidazole-sensitive isolates ranged from 92 to 98% and 95 to 98%, respectively, compared to that of
H. pylori
J99 (MIC, 1 μg/ml). All strains with high-level metronidazole resistance (MICs, 128 μg/ml) contained premature truncation of both RdxA and FrxA caused by nonsense and/or frameshift mutations. Strains with intermediate resistance to metronidazole (MICs, 32 to 64 μg/ml) contained a single premature truncation and/or altered RdxA and FrxA caused by nonsense, frameshift, and unique missense mutations. The low-level metronidazole-resistant strains (MICs, 8 μg/ml) contained unique missense mutations in FrxA but no specific changes in RdxA. The results demonstrate that alterations in both the
rdxA
and
frxA
genes are required for moderate and high-level metronidazole resistance and that metronidazole resistance that develops during anti-
H. pylori
therapy containing metronidazole is most likely to involve a single sensitive strain infection rather than a coinfection with a metronidazole-resistant strain.
In Vitro Antifungal Activities of the New Triazole UR-9825 against Clinically Important Filamentous Fungi
Authors: Capilla Javier , Ortoneda Montserrat , Pastor Francisco Javier , Guarro Josep 
Published: July 2002

ABSTRACT

We used a modified reference microdilution method (the M-38P method) to evaluate the in vitro activities of the new triazole UR-9825 in comparison with those of amphotericin B against 77 strains of opportunistic filamentous fungi. UR-9825 was clearly more active than amphotericin B against all fungi except
Fusarium solani
and
Scytalidium
spp. Notably, UR-9825 had low MICs for
Aspergillus fumigatus
and
Paecilomyces lilacinus
(MICs at which 90% of isolates are inhibited, 0.125 μg/ml for both species).
Type II Topoisomerase Quinolone Resistance-Determining Regions of
Aeromonas caviae
, A. hydrophila, and
A. sobria
Complexes and Mutations Associated with Quinolone Resistance
Authors: Goñi-Urriza Marisol , Arpin Corinne , Capdepuy Michèle , Dubois Véronique , Caumette Pierre , Quentin Claudine 
Published: July 2002

ABSTRACT

Most
Aeromonas
strains isolated from two European rivers were previously found to be resistant to nalidixic acid. In order to elucidate the mechanism of this resistance, 20 strains of
Aeromonas caviae
(
n
= 10),
A. hydrophila
(
n
= 5), and
A. sobria
(
n
= 5) complexes, including 3 reference strains and 17 environmental isolates, were investigated. Fragments of the
gyrA
,
gyrB
,
parC
, and
parE
genes encompassing the quinolone resistance-determining regions (QRDRs) were amplified by PCR and sequenced. Results obtained for the six sensitive strains showed that the GyrA, GyrB, ParC, and ParE QRDR fragments of
Aeromonas
spp. were highly conserved (≥96.1% identity), despite some genetic polymorphism; they were most closely related to those of
Vibrio
spp.,
Pseudomonas
spp., and members of the family
Enterobacteriaceae
(72.4 to 97.1% homology). All 14 environmental resistant strains carried a point mutation in the GyrA QRDR at codon 83, leading to the substitution Ser-83→Ile (10 strains) or Ser-83→Arg. In addition, seven strains harbored a mutation in the ParC QRDR either at position 80 (five strains), generating a Ser-80→Ile (three strains) or Ser-80→Arg change, or at position 84, yielding a Glu-84→Lys modification. No amino acid alterations were discovered in the GyrB and ParE QRDRs. Double
gyrA-parC
missense mutations were associated with higher levels of quinolone resistance compared with the levels associated with single
gyrA
mutations. The most resistant strains probably had an additional mechanism(s) of resistance, such as decreased accumulation of the drugs. Our data suggest that, in mesophilic
Aeromonas
spp., as in other gram-negative bacteria, gyrase and topoisomerase IV are the primary and secondary targets for quinolones, respectively.
Efficacy of Antifungal Therapy in a Nonneutropenic Murine Model of Zygomycosis
Authors: Dannaoui Eric , Mouton Johan W. , Meis Jacques F. G. M. , Verweij Paul E. 
Published: July 2002

ABSTRACTThree isolates of zygomycetes belonging to three different genera (Rhizopus microsporus,Absidia corymbifera, andApophysomyces elegans) were used to produce a disseminated infection in nonimmunocompromised mice. The therapeutic efficacy of amphotericin B, given intraperitoneally at doses ranging from 0.5 to 4.5 mg/kg of body weight/day, oral itraconazole at 100 mg/kg/day, and oral terbinafine at 150 mg/kg/day was evaluated in this model. The markers of antifungal efficacy were the median survival time, the mortality rate, and the percentage of infected organs. Organ culture was performed along with microscopic direct examinations of tissues to assess the presence of an active infection. An acute and lethal infection was obtained in untreated mice challenged with each of the three strains. The data obtained for direct examinations and qualitative cultures indicate that, due to the nonseptate nature of the hyphae, each technique gives different information and should be used together with the others. Against all three strains, amphotericin B yielded a 90 to 100% survival rate. Itraconazole was inactive againstR. microsporusbut significantly reduced mortality in mice infected withA. corymbiferaorA. elegans.Terbinafine had no beneficial effects againstR. microsporusandA. corymbiferadespite documented absorption of the drug. Overall, only limited correlations were observed between MICs determined in vitro and in vivo efficacy of the drugs. The efficacy of itraconazole in these models of zygomycosis suggests that this drug, as well as the new azole compounds presently under development, warrants close evaluation.
Characterization of Reutericyclin Produced by
Lactobacillus reuteri
LTH2584
Authors: Gänzle Michael G. , Höltzel Alexandra , Walter Jens , Jung Günther , Hammes Walter P. 
Published: July 2002

ABSTRACT

Lactobacillus reuteri
LTH2584 exhibits antimicrobial activity that can be attributed neither to bacteriocins nor to the production of reuterin or organic acids. We have purified the active compound, named reutericyclin, to homogeneity and characterized its antimicrobial activity. Reutericyclin exhibited a broad inhibitory spectrum including
Lactobacillus
spp.,
Bacillus subtilis
,
B. cereus
,
Enterococcus faecalis
,
Staphylococcus aureus
, and
Listeria innocua
. It did not affect the growth of gram-negative bacteria; however, the growth of lipopolysaccharide mutant strains of
Escherichia coli
was inhibited. Reutericyclin exhibited a bactericidal mode of action against
Lactobacillus sanfranciscensis
,
Staphylococcus aureus
, and
B. subtilis
and triggered the lysis of cells of
L. sanfranciscensis
in a dose-dependent manner. Germination of spores of
B. subtilis
was inhibited, but the spores remained unaffected under conditions that do not permit germination. The fatty acid supply of the growth media had a strong effect on reutericyclin production and its distribution between producer cells and the culture supernatant. Reutericyclin was purified from cell extracts and culture supernatant of
L. reuteri
LTH2584 cultures grown in mMRS by solvent extraction, gel filtration, RP-C
8
chromatography, and anion-exchange chromatography, followed by rechromatography by reversed-phase high-pressure liquid chromatography. Reutericyclin was characterized as a negatively charged, highly hydrophobic molecule with a molecular mass of 349 Da. Structural characterization (A. Höltzel, M. G. Gänzle, G. J. Nicholson, W. P. Hammes, and G. Jung, Angew. Chem. Int. Ed. 39:2766–2768, 2000) revealed that reutericyclin is a novel tetramic acid derivative. The inhibitory activity of culture supernatant of
L. reuteri
LTH2584 corresponded to that of purified as well as synthetic reutericyclin.
Bacterial Origin and Community Composition in the Barley Phytosphere as a Function of Habitat and Presowing Conditions
Authors: Normander Bo , Prosser Jim I. 
Published: July 2002

ABSTRACT

An understanding of the factors influencing colonization of the rhizosphere is essential for improved establishment of biocontrol agents. The aim of this study was to determine the origin and composition of bacterial communities in the developing barley (
Hordeum vulgare
) phytosphere, using denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA genes amplified from extracted DNA. Discrete community compositions were identified in the endorhizosphere, rhizoplane, and rhizosphere soil of plants grown in an agricultural soil for up to 36 days. Cluster analysis revealed that DGGE profiles of the rhizoplane more closely resembled those in the soil than the profiles found in the root tissue or on the seed, suggesting that rhizoplane bacteria primarily originated from the surrounding soil. No change in bacterial community composition was observed in relation to plant age. Pregermination of the seeds for up to 6 days improved the survival of seed-associated bacteria on roots grown in soil, but only in the upper, nongrowing part of the rhizoplane. The potential occurrence of skewed PCR amplification was examined, and only minor cases of PCR bias for mixtures of two different DNA samples were observed, even when one of the samples contained plant DNA. The results demonstrate the application of culture-independent, molecular techniques in assessment of rhizosphere bacterial populations and the importance of the indigenous soil population in colonization of the rhizosphere.