bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiotic-Induced Enterococcal Expansion in the Mouse Intestine Occurs throughout the Small Bowel and Correlates Poorly with Suppression of Competing Flora
Authors: Laktic̀ová Viera , Hutton-Thomas Rebecca , Meyer Matthew , Gurkan Evren , Rice Louis B. 
Published: August 2006

ABSTRACT

To test the hypothesis that establishing gastrointestinal colonization with multiresistant
Enterococcus faecium
(VRE) C68 results from expansion of the enterococcal population in the upper small bowel, we compared VRE quantities recovered from the proximal, middle, and distal segments of the small bowel from mice treated with different antimicrobial agents. Antibiotics associated with high-level VRE fecal colonization (cefotetan, ceftriaxone, clindamycin, and ticarcillin-clavulanic acid) increased VRE quantities in all small-bowel segments, whereas cefepime and piperacillin-tazobactam did not. Enterococcal expansion did not correlate with reductions in numbers of native gram-negative or anaerobic flora. Green fluorescence protein-expressing
E. faecium
bacteria were found adjacent to the small bowel epithelial lining in colonized mice. These data indicate that enterococcal bowel colonization begins within the proximal small bowel and does not correlate with inhibition of other cultivable flora. Host or enterococcal factors induced by exposures to certain antibiotics may play a role in facilitating
E. faecium
colonization of the mammalian gastrointestinal tract.
Replicon Typing of Plasmids Carrying CTX-M or CMY β-Lactamases Circulating among
Salmonella
and
Escherichia coli
Isolates
Authors: Hopkins Katie L. , Liebana Ernesto , Villa Laura , Batchelor Miranda , Threlfall E. John , Carattoli Alessandra 
Published: August 2006

ABSTRACT

Replicon typing of plasmids carrying
bla
CTX-M
or
bla
CMY
β-lactamase genes indicates a predominance of I1 and A/C replicons among
bla
CMY
-carrying plasmids and five different plasmid scaffolds associated with the different types of
bla
CTX-M
genes (I1, FII, HI2, K, and N). These results demonstrate the association of certain β-lactamase genes with specific plasmid backbones.
Prior Antibacterial Peptide-Mediated Inhibition of Protein Folding in Bacteria Mutes Resistance Enzymes
Authors: Otvos Laszlo , de Olivier Inacio Vanessa , Wade John D. , Cudic Predrag 
Published: August 2006

ABSTRACT
The antimicrobial activity of amoxicillin against TEM-1-expressing strains could be fully recovered when bacteria were preincubated with sublethal doses of an antibacterial peptide derivative. Assays with the simultaneous administration of antibiotics or synergy assays with kanamycin or ciprofloxacin, where resistance development does not involve properly folded proteins, failed to yield similar results.
Successful Therapy of Experimental Endocarditis Caused by Vancomycin-Resistant
Staphylococcus aureus
with a Combination of Vancomycin and β-Lactam Antibiotics
Authors: Fox Paige M. , Lampen Russell J. , Stumpf Katrina S. , Archer Gordon L. , Climo Michael W. 
Published: August 2006

ABSTRACT

VRS1 is the first isolated strain of vancomycin-resistant
Staphylococcus aureus
(VRSA) found to carry the
vanA
gene complex previously described in
Enterococcus
. Under vancomycin pressure, VRS1 makes aberrant cell walls consisting of stem tetrapeptide and depsipeptide that lack the terminal
d
-Ala-
d
-Ala residues targeted by vancomycin. Previous data have suggested that this aberrant cell wall is not cross-linked by PBP2a, the enzyme responsible for cell wall transpeptidation in the presence of β-lactam antibiotics. We examined the efficacy of treating VRS1 with a combination of vancomycin and β-lactam antibiotics in vitro and in vivo. We found that the MIC of oxacillin for VRS1 decreased from >256 μg/ml to <1 μg/ml in the presence of vancomycin. Using the rabbit model of endocarditis, we treated VRS1-infected rabbits with nafcillin alone, vancomycin alone, or a combination of nafcillin and vancomycin. Treatment with nafcillin in combination with vancomycin cleared bloodstream infections within 24 h and sterilized 12/13 spleens (92%), as well as 8/13 kidneys (62%), following 3 days of treatment. Mean aortic valve vegetation counts were reduced 3.48 log
10
CFU/g with the combination therapy (compared to untreated controls) and were significantly lower than with either vancomycin or nafcillin given alone. VRS1 was extremely virulent in this model, as no untreated rabbits survived the 3-day trial. Treatment of clinical infections due to VRSA with the combination of vancomycin and β-lactams may be an option, based on these results.
Identification of RNase 8 as a Novel Human Antimicrobial Protein
Authors: Rudolph Bente , Podschun Rainer , Sahly Hany , Schubert Sabine , Schröder Jens M. , Harder Jürgen 
Published: August 2006

ABSTRACTThe antimicrobial activity of the human RNase A superfamily member RNase 8 was evaluated. Recombinant RNase 8 exhibited broad-spectrum microbicidal activity against potential pathogenic microorganisms (including multidrug-resistant strains) at micro- to nanomolar concentrations. Thus, RNase 8 was identified as a novel antimicrobial protein and may contribute to host defense.
Molecular Characterization of Resistance to Macrolides in
Bartonella henselae
Authors: Biswas Silpak , Raoult Didier , Rolain Jean-Marc 
Published: August 2006

ABSTRACT

We selected in vitro erythromycin-resistant strains of
Bartonella henselae
. The mutants obtained had point mutations in domain V of 23S rRNA and/or in ribosomal protein L4. One lymph node of a patient with cat-scratch disease had such a mutation in 23S rRNA, suggesting that natural resistant strains may infect humans.
Genetic Environment of Quinolone Resistance Gene
qnrB2
in a Complex
sul1
-Type Integron in the Newly Described
Salmonella enterica
Serovar Keurmassar
Authors: Garnier Fabien , Raked Nabil , Gassama Amy , Denis François , Ploy Marie-Cécile 
Published: August 2006

ABSTRACT

A
qnrB2
determinant was described for a new complex
sul1
-type integron from
Salmonella enterica
serovar Keurmassar. The genetic structure contained two class 1 integrons surrounding two common regions (CRs) separated by a partial 3′ conserved segment. The
qnrB2
gene is adjacent to the first CR.
NIM811, a Cyclophilin Inhibitor, Exhibits Potent In Vitro Activity against Hepatitis C Virus Alone or in Combination with Alpha Interferon
Authors: Ma Sue , Boerner Joanna E. , TiongYip ChoiLai , Weidmann Beat , Ryder Neil S. , Cooreman Michael P. , Lin Kai 
Published: August 2006

ABSTRACT

Host factors involved in viral replication are potentially attractive antiviral targets that are complementary to specific inhibitors of viral enzymes, since resistant mutations against the latter are likely to emerge during long-term treatment. It has been reported recently that cyclosporine, which binds to a family of cellular proteins, cyclophilins, inhibits hepatitis C virus (HCV) replication in vitro. Here, the activities of various cyclosporine derivatives were evaluated in the HCV replicon system. There was a strong correlation between the anti-HCV activity and cyclophilin-binding affinity of these compounds. Of these, NIM811 has been selected as a therapeutic candidate for HCV infection, since it binds to cyclophilins with higher affinity than cyclosporine but is devoid of the significant immunosuppressive activity associated with cyclosporine. NIM811 induced a concentration-dependent reduction of HCV RNA in the replicon cells with a 50% inhibitory concentration of 0.66 μM at 48 h. Furthermore, a greater than three-log
10
viral RNA reduction was achieved after treating the cells with as little as 1 μM of NIM811 for 9 days. In addition, the combination of NIM811 with alpha interferon significantly enhanced anti-HCV activities without causing any increase of cytotoxicity. Taken together, these promising in vitro data warrant clinical investigation of NIM811, an inhibitor of novel mechanism, for the treatment of hepatitis C.
In Vitro Activity of Tigecycline against Multiple-Drug-Resistant, Including Pan-Resistant, Gram-Negative and Gram-Positive Clinical Isolates from Greek Hospitals
Authors: Souli Maria , Kontopidou Flora V. , Koratzanis Evangelos , Antoniadou Anastasia , Giannitsioti Efthimia , Evangelopoulou Pinelopi , Kannavaki Sofia , Giamarellou Helen 
Published: August 2006

ABSTRACT

The in vitro activities of tigecycline and selected antimicrobials were evaluated against a variety of multiple-drug-resistant clinical isolates, including extended-spectrum β-lactamase- and/or metallo-β-lactamase-producing gram-negative strains, colistin-resistant strains, vancomycin- and/or linezolid-resistant enterococci, and methicillin-resistant
Staphylococcus aureus
(MRSA). Tigecycline showed excellent activity against a collection of difficult-to-treat pathogens currently encountered in the hospital setting.
Evolution and Global Dissemination of Macrolide-Resistant Group A Streptococci
Authors: Robinson D. Ashley , Sutcliffe Joyce A. , Tewodros Wezenet , Manoharan Anand , Bessen Debra E. 
Published: August 2006

ABSTRACT

Macrolide-resistant group A streptococci (MRGAS) have been recovered from many countries worldwide. However, the strain typing information that is available has been insufficient for estimating the total number of macrolide-resistant clones, their geographic distributions, and their evolutionary relationships. In this study, sequence-based strain typing was used to characterize 212 MRGAS isolates from 34 countries. Evaluation of clonal complexes,
emm
type, and resistance gene content [
erm
(A),
erm
(B),
mef
(A), and undefined] indicate that macrolide resistance was acquired by GAS organisms via ≥49 independent genetic events. In contrast to other collections of mostly susceptible GAS, genetic diversification of MRGAS clones has occurred primarily by mutation rather than by recombination. Twenty-two MRGAS clonal complexes were recovered from more than one continent; intercontinental strains represent nearly 80% of the MRGAS isolates under study. The findings suggest that horizontal transfer of macrolide resistance genes to numerous genetic backgrounds and global dissemination of resistant clones and their descendants are both major components of the present-day macrolide resistance problem found within this species.
Generation of a Reporter Cell Line for Detection of Infectious Varicella-Zoster Virus and Its Application to Antiviral Studies
Authors: Wang Guan-Qing , Suzutani Tatsuo , Yamamoto Yumiko , Fukui Yoshiko , Nozawa Naoki , Schmid D. Scott , Kurane Ichiro , Inoue Naoki 
Published: August 2006

ABSTRACT
To simplify the titration of infectious varicella-zoster virus (VZV), we generated a reporter cell line that produced luciferase in a dose-dependent manner upon infection with cell-free VZV. A few VZV-infected cells were detectable by coculturing with the cell line. We demonstrated the usefulness of the cell line for antiviral studies.
Isolates with Low-Level Vancomycin Resistance Associated with Persistent Methicillin-Resistant
Staphylococcus aureus
Bacteremia
Authors: Howden Benjamin P. , Johnson Paul D. R. , Ward Peter B. , Stinear Timothy P. , Davies John K. 
Published: August 2006

ABSTRACT

Low-level vancomycin-resistant
Staphylococcus aureus
(vancomycin-intermediate
S. aureus
[VISA] and heterogenous VISA [hVISA]) is increasingly reported and leads to glycopeptide treatment failure. Various phenotypic features have been reported for these isolates, but the genetic changes leading to hVISA and VISA have yet to be clearly determined. We assessed phenotypic, antibiotic resistance, and genomic changes by using genomic DNA microarray comparison and sequencing of selected loci in five pairs of clinical hVISA/VISA strains and the initial methicillin-resistant
Staphylococcus aureus
(MRSA) isolates obtained prior to vancomycin therapy. The isolates were from adult patients in Australia and New Zealand who had persistent MRSA bacteremia (>7 days) while receiving vancomycin therapy. In all cases, the initial isolates were found to be fully vancomycin-susceptible
Staphylococcus aureus
(VSSA). The hVISA/VISA phenotype was associated with increased cell wall thickness, reduced autolytic activity in four of five hVISA/VISA strains, and a striking reduction in biofilm formation compared to the parent strains in all pairs. All five pairs appeared to be isogenic, and genomic DNA microarray comparison suggested that major genetic changes are not required for the development of the resistant phenotype in these strains. No sequence differences were found in the
agr
locus or the
tcaRA
genes for any pair, but a marked reduction in RNAIII expression was found in four pairs. In summary, hVISA/VISA arises from fully VSSA during persistent infection that fails to respond to glycopeptide therapy and is associated with significant phenotypic changes, including a marked reduction in biofilm-forming ability. These clinically derived pairs of isolates will be a useful resource to elucidate the genetic mechanism of resistance in hVISA/VISA strains.
Plasmid-Mediated Imipenem-Hydrolyzing Enzyme KPC-2 among Multiple Carbapenem-Resistant
Escherichia coli
Clones in Israel
Authors: Navon-Venezia Shiri , Chmelnitsky Inna , Leavitt Azita , Schwaber Mitchell J. , Schwartz David , Carmeli Yehuda 
Published: August 2006

ABSTRACT

Carbapenem resistance in
Escherichia coli
is rare. We report four genetically unrelated carbapenem-resistant
E. coli
isolates cultured from four patients hospitalized in Tel Aviv Medical Center. PCR, sequencing, and Southern blot analysis identified KPC-2 as the imipenem-hydrolyzing enzyme in all four strains, carried on different plasmids with a possible common origin. This is the first discovery of KPC-2 in
E. coli
and the first report of this enzyme originating outside the United States.
In Vitro Activities of Itraconazole, Methiazole, and Nitazoxanide versus
Echinococcus multilocularis
Larvae
Authors: Reuter Stefan , Manfras Burkhard , Merkle Marion , Härter Georg , Kern Peter 
Published: August 2006

ABSTRACT

Albendazole (ABZ) and mebendazole are the only drugs licensed for treatment of human alveolar echinococcosis. In order to augment the armamentarium against this deadly disease, we tested a series of drugs for their efficacy against
Echinococcus multilocularis
larvae.
E. multilocularis
larvae grown intraperitoneally in Mongolian gerbils were transferred into tissue culture. Vesicles budded from the tissue blocks and after 6 weeks, drugs were added, and the effect on the vesicles was observed. We tested the following drugs at various concentrations: ABZ, artemether, caspofungin, itraconazole (ITZ), ivermectin, methiazole (MTZ), miltefosine, nitazoxanide (NTZ), rifampin, and trimethoprim-sulfamethoxazole. ABZ, ITZ, MTZ, and NTZ effectively destroyed parasite vesicles in this in vitro culture system. At high NTZ doses of 10 μg/ml, disintegration of all vesicles was observed after 7 days and was significantly more rapid than with ABZ at equal concentrations (21 days). After drug discontinuation, regrowth of vesicles occurred between 7 and 14 days for all four drugs, indicating a parasitostatic effect. Combination treatment with NTZ-ABZ at concentrations between 1 and 10 μg/ml for either 3 weeks, 3 months, or 6 months yielded no vesicle regrowth during 8 months after drug discontinuation. The treated larval tissue was injected intraperitoneally into gerbils, and no regrowth of larval tissue was observed, suggesting a parasitocidal effect after combined treatment. ITZ, MTZ, and NTZ are potent inhibitors of larval growth, although they proved to be parasitostatic only. The combination of NTZ plus ABZ was parasitocidal in vitro. Animal experiments are warranted for studies of dose, toxicity, and drug interactions.
Rapid Degradation of Oseltamivir Phosphate in Clinical Samples by Plasma Esterases
Authors: Lindegardh Niklas , Davies Geraint R. , Hien Tran Tinh , Farrar Jeremy , Singhasivanon Pratap , Day Nicholas P. J. , White Nicholas J. 
Published: August 2006

ABSTRACT
The anti-influenza drug oseltamivir is an ester prodrug activated by hepatic carboxylesterases. Plasma esterases also convert up to 31.8% of the parent compound to the active metabolite after 4 h ex vivo, with wide interindividual variation. This source of error is removed by adding the esterase inhibitor dichlorvos to blood collection tubes.
In Vitro Activity of Daptomycin against Methicillin-Resistant
Staphylococcus aureus
, Including Heterogeneously Glycopeptide-Resistant Strains
Authors: Diederen Bram M. W. , van Duijn Inge , Willemse Piet , Kluytmans Jan A. J. W. 
Published: August 2006

ABSTRACT

The purpose of the present study was to assess the in vitro activity of daptomycin against a well-defined collection of methicillin-resistant
Staphylococcus aureus
(MRSA) isolates (
n
= 98), including heterogeneously glycopeptide-resistant MRSA (hGISA) strains. Susceptibility testing was performed by using the Etest system. Daptomycin was potent against both glycopeptide-susceptible and hGISA strains.
Mode of Transposition and Expression of 16S rRNA Methyltransferase Gene
rmtC
Accompanied by IS
Ecp1
Authors: Wachino Jun-ichi , Yamane Kunikazu , Kimura Kouji , Shibata Naohiro , Suzuki Satowa , Ike Yasuyoshi , Arakawa Yoshichika 
Published: August 2006

ABSTRACT

A newly identified 16S rRNA methyltransferase gene,
rmtC
, was accompanied by an IS
Ecp1
element at its 5′ end. This IS
Ecp1
element, which contained a transposase gene,
tnpA
, provided a promoter activity for expression of the adjacent
rmtC
; and this structure enabled the
rmtC
gene to be transposed onto another plasmid in
Escherichia coli
.
Escape of
Candida
from Caspofungin Inhibition at Concentrations above the MIC (Paradoxical Effect) Accomplished by Increased Cell Wall Chitin; Evidence for β-1,6-Glucan Synthesis Inhibition by Caspofungin
Authors: Stevens David A. , Ichinomiya Masayuki , Koshi Yukako , Horiuchi Hiroyuki 
Published: August 2006

ABSTRACT

Concentrations above the MIC of caspofungin allow growth of some
Candida
isolates. A strain demonstrating paradoxical growth was grown in the presence and absence of caspofungin, and the cell wall content was analyzed. β-1,3-Glucan declined 81% in the presence of caspofungin, as expected. β-1,6-Glucan declined 73%. Chitin increased 898%, demonstrating a mechanism for paradoxical growth—a rapid shift in the key polymer.
In Vitro Activities of DA-7157 and DA-7218 against
Mycobacterium tuberculosis
and
Nocardia brasiliensis
Authors: Vera-Cabrera Lucio , Gonzalez Eva , Rendon Adrian , Ocampo-Candiani Jorge , Welsh Oliverio , Velazquez-Moreno Victor M. , Hak Choi Sung , Molina-Torres Carmen 
Published: August 2006

ABSTRACT

The in vitro activities of DA-7157, a novel oxazolidinone, against clinical isolates of
Nocardia brasiliensis
and
Mycobacterium tuberculosis
were determined. Equal MIC
50
s and MIC
90
s (0.25 and 0.5 μg/ml, respectively) were found for susceptible and multidrug-resistant isolates of
M. tuberculosis
. The
N. brasiliensis
isolates showed an MIC
90
of 1 μg/ml and an MIC
50
of 1 μg/ml. The DA-7157 prodrug, DA-7218, exhibited similar MICs for
M. tuberculosis
but fivefold-higher MICs for
N. brasiliensis
.
Are Broad-Spectrum Fluoroquinolones More Likely To Cause
Clostridium difficile
-Associated Disease?
Authors: Dhalla Irfan A. , Mamdani Muhammad M. , Simor Andrew E. , Kopp Alex , Rochon Paula A. , Juurlink David N. 
Published: August 2006

ABSTRACT

Limited evidence suggests that broad-spectrum fluoroquinolones such as gatifloxacin and moxifloxacin are more likely to cause
Clostridium difficile
-associated disease than levofloxacin. In a population-based case-control study of outpatients prescribed fluoroquinolones, we found no increased risk of
C. difficile
-associated disease requiring hospitalization among patients prescribed gatifloxacin or moxifloxacin compared to levofloxacin.
Eosin B as a Novel Antimalarial Agent for Drug-Resistant
Plasmodium falciparum
Authors: Massimine Kristen M. , McIntosh Michael T. , Doan Lanxuan T. , Atreya Chloé E. , Gromer Stephan , Sirawaraporn Worachart , Elliott David A. , Joiner Keith A. , Schirmer R. Heiner , Anderson Karen S. 
Published: August 2006

ABSTRACT

4′,5′-Dibromo-2′,7′-dinitrofluorescein, a red dye commonly referred to as eosin B, inhibits
Toxoplasma gondii
in both enzymatic and cell culture studies with a 50% inhibitory concentration (IC
50
) of 180 μM. As a non-active-site inhibitor of the bifunctional
T. gondii
dihydrofolate reductase-thymidylate synthase (DHFR-TS), eosin B offers a novel mechanism for inhibition of the parasitic folate biosynthesis pathway. In the present study, eosin B was further evaluated as a potential antiparasitic compound through in vitro and cell culture testing of its effects on
Plasmodium falciparum
. Our data revealed that eosin B is a highly selective, potent inhibitor of a variety of drug-resistant malarial strains, with an average IC
50
of 124 nM. Furthermore, there is no indication of cross-resistance with other clinically utilized compounds, suggesting that eosin B is acting via a novel mechanism. The antimalarial mode of action appears to be multifaceted and includes extensive damage to membranes, the alteration of intracellular organelles, and enzymatic inhibition not only of DHFR-TS but also of glutathione reductase and thioredoxin reductase. In addition, preliminary studies suggest that eosin B is also acting as a redox cycling compound. Overall, our data suggest that eosin B is an effective lead compound for the development of new, more effective antimalarial drugs.
Mechanism-Based Pharmacodynamic Models of Fluoroquinolone Resistance in
Staphylococcus aureus
Authors: Chung Philip , McNamara Patrick J. , Campion Jeffrey J. , Evans Martin E. 
Published: August 2006

ABSTRACT

Pharmacodynamic modeling from earlier experiments in which two ciprofloxacin-susceptible
Staphylococcus aureus
strains and their corresponding resistant
grlA
mutants were exposed to a series of ciprofloxacin (J. J. Campion, P. J. McNamara, and M. E. Evans, Antimicrob. Agents Chemother. 49:209-219, 2005) and levofloxacin (J. J. Campion et al., Antimicrob. Agents Chemother. 49:2189-2199, 2005) pharmacokinetic profiles in an in vitro system indicated that the subpopulation-specific estimated maximal killing rate constants were similar for both agents, suggesting a common mechanism of action. We propose two novel pharmacodynamic models that assign mechanisms of action to fluoroquinolones (growth inhibition or death stimulation) and compare the abilities of these models and two other maximum effect models (net effect and MIC based) to describe and predict the changes in the population dynamics observed during our previous in vitro system experiments with ciprofloxacin. A high correlation between predicted and observed viable counts was observed for all models, but the best fits, as assessed by diagnostic tests, and the most precise parameter estimates were obtained with the growth inhibition and net effect models. All models, except the death stimulation model, correctly predicted that resistant subpopulations would not emerge when a high-density culture was exposed to a high initial concentration designed to rapidly eradicate low-level-resistant
grlA
mutants. Additional experiments are necessary to elucidate which of the proposed mechanistic models best characterizes the antibacterial effects of fluoroquinolone antimicrobial agents.
Use of Nonlinear Mixed-Effects Analysis for Improved Precision of Early Pharmacodynamic Measures in Tuberculosis Treatment
Authors: Davies Geraint R. , Brindle Richard , Khoo Saye H. , Aarons Leon J. 
Published: August 2006

ABSTRACT
Nonlinear mixed-effects analysis of serial sputum colony-counting data supports the existence of two bacillary subpopulations in sputum, eliminated at different rates. It distinguishes between combination regimens, removes bias, and greatly improves precision, with significant implications for the analysis of surrogate endpoints of “sterilization” in the development of new antituberculosis regimens.