bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quinolone Efflux Pumps Play a Central Role in Emergence of Fluoroquinolone Resistance in
Streptococcus pneumoniae
Authors: Jumbe Nelson L. , Louie Arnold , Miller Michael H. , Liu Weiguo , Deziel Mark R. , Tam Vincent H. , Bachhawat Reetu , Drusano George L. 
Published: December 2005

ABSTRACT

The preferential use of older antimicrobial agents is, in general, sound public health policy and is meant to maintain susceptibility to newer agents. In the case of fluoroquinolones, however, this strategy is flawed and may actually hasten the spread of
Streptococcus pneumoniae
strains resistant to newer members of the class. In a mouse thigh infection model, we were unable to isolate clones of pneumococci resistant to the newer fluoroquinolone levofloxacin at 2 × or 4 × the baseline MIC. An initial exposure in vivo to the older agent, ciprofloxacin, allowed straightforward selection of clones resistant to levofloxacin in a subsequent experiment. The original ciprofloxacin exposure generated clones without changes in the
parC
/
E
and
gyrA
/
B
quinolone target sites almost exclusively but did allow overexpression of a reserpine-responsive pump. While this caused only minimal change in the levofloxacin MIC (0.6 mg/liter to 0.8 mg/liter), it allowed a major change in the mutational frequency to resistance for levofloxacin (<1/10
8.5
to approximately 1/10
4.5
), which allowed levofloxacin-resistant clones to be isolated in a subsequent in vivo experiment. The reason underlying ciprofloxacin's propensity to select for pump-overexpressed clones is likely related to its hydrophilicity. To preserve the susceptibility of
Streptococcus pneumoniae
to newer members of the class of quinolones, use of ciprofloxacin for community-acquired respiratory infections should be minimized.
Computer-Aided Design of Agents That Inhibit the
cep
Quorum-Sensing System of
Burkholderia cenocepacia
Authors: Riedel Kathrin , Köthe Manuela , Kramer Bernd , Saeb Wael , Gotschlich Astrid , Ammendola Aldo , Eberl Leo 
Published: December 2005

ABSTRACT

Recent research has provided evidence that interference with bacterial cell-to-cell signaling is a promising strategy for the development of novel antimicrobial agents. Here we report on the computer-aided design of novel compounds that specifically inhibit an
N
-acyl-homoserine lactone-dependent communication system that is widespread among members of the genus
Burkholderia
. This genus comprises more than 30 species, many of which are important pathogens of animals and humans. Over the past few years, several
Burkholderia
species, most notably
Burkholderia cenocepacia
, have emerged as important opportunistic pathogens causing severe pulmonary deterioration in persons with cystic fibrosis. As efficient treatment of
Burkholderia
infections is hampered by the inherent resistance of the organisms to a large range of antibiotics, novel strategies for battling these pathogens need to be developed. Here we show that compounds targeting the
B. cenocepacia
signaling system efficiently inhibit the expression of virulence factors and attenuate the pathogenicity of the organism.
Distinct Antifungal Mechanisms: β-Defensins RequireCandida albicansSsa1 Protein, while Trk1p Mediates Activity of Cysteine-Free Cationic Peptides
Authors: Vylkova Slavena , Li Xuewei S. , Berner Jennifer C. , Edgerton Mira 
Published: December 2005

ABSTRACTSalivary histatin 5 (Hst 5) kills the fungal pathogenCandida albicansvia a multistep process which includes binding to Ssa1/2 proteins on the cell surface and requires the TRK1 potassium transporter. Hst 5-induced membrane permeability to propidium iodide (PI) was nearly abolished in strain CaTK1 (TRK1/trk1), suggesting that Hst 5-induced influx of PI is via Trk1p. To explore the functional role of Trk1p in the mechanism of other antifungal peptides, we evaluated candidacidal activity and PI uptake in wild-type strain CaTK2 (TRK1/TRK1) and strain CaTK1 following treatment with lactoferricin 11 (LFcn 11), bactenecin 16 (BN 16), and virion-associated protein VPR 12. Strain CaTK1 was resistant to killing with these peptides (VPR 12 > LFcn 11 > BN 16), showing the requirement of Trk1p for fungicidal activity. In contrast, human neutrophil defensin 1 (HNP-1), human β-defensin 2 (hBD-2), and hBD-3 effects on viability of and membrane permeability to PI were not different between mutant and wild-type strains, clearly showing that their candidacidal mechanism does not involve Trk1p as a functional effector. To test whether defensins require binding toCandidasurface Ssa1/2 proteins for their activity, we measured the killing effectiveness inSSA1/2mutant strains. Both hBD-2 and hBD-3, but not HNP-1, exhibited reduced killing ofssa1Δ andssa2Δ strains compared to the wild type, showing that Ssa1 and Ssa2 proteins are required for their fungicidal activity. These results demonstrate that (i) Trk1p mediates candidacidal activities of cysteine-free peptides, but not of defensins, and (ii) hBD-2 and hBD-3, but not HNP-1, require Ssa1/2p for antifungal activity.
VraSR Two-Component Regulatory System and Its Role in Induction of
pbp2
and
vraSR
Expression by Cell Wall Antimicrobials in
Staphylococcus aureus
Authors: Yin Shaohui , Daum Robert S. , Boyle-Vavra Susan 
Published: December 2005

ABSTRACT

The VraS/VraR two-component system (VraSR) regulates transcriptional induction of penicillin-binding protein 2 (encoded by
pbp2
) by vancomycin in
Staphylococcus aureus
. We have now defined the
vraSR
operon and determined that its induction by β-lactams as well as by vancomycin is autoregulated. Induction of the
pbp2
and
vraSR
operons by β-lactams and related compounds within 1 hour after exposure to the antimicrobials was dependent on
vraS
. However, when a disk diffusion assay that can detect induction of genes over an extended time period was used, induction of the
pbp2
operon was mediated by some β-lactams, including oxacillin; this induction was independent of
vraS
.
Microdialysis Study of Imipenem Distribution in the Intraperitoneal Fluid of Rats with or without Experimental Peritonitis
Authors: Lefeuvre Sandrine , Marchand Sandrine , Lamarche Isabelle , Mimoz Olivier , Couet William 
Published: December 2005

ABSTRACT

The purpose of this study was to extend the use of microdialysis to the investigation of antibiotic distribution into the intraperitoneal fluid of rats with or without peritonitis. Microdialysis probes were inserted into the jugular vein and peritoneal cavity of control rats or rats with intra-abdominal sepsis (
n
= 8 in each group) induced by cecal ligation and punctures. Imipenem (IPM) probe recoveries were determined in each rat by retrodialysis by drug. IPM was infused intravenously at a dose of 30 mg · kg
−1
over 30 min, microdialysis samples were collected for 120 min, and IPM concentrations were determined by high-performance liquid chromatography. Intraperitoneal infection had no statistically significant effect on IPM clearance (11.9 ± 2.3 ml · min
−1
· kg
−1
in control rats versus 10.9 ± 2.1 ml · min
−1
· kg
−1
in rats with peritonitis) or the volume of distribution (296 ± 47 ml · kg
−1
in control rats versus 310 ± 49 ml · kg
−1
in rats with peritonitis). IPM concentration profiles in intraperitoneal fluid and blood were virtually superimposed in control rats, whereas in infected animals, the mean intraperitoneal IPM concentrations were apparently slightly lower than corresponding blood levels. However, the areas under the concentration-versus-time curve estimated in intraperitoneal fluid and blood were not significantly different in both groups, with the corresponding ratios close to unity (1.01 ± 0.19 and 0.89 ± 0.28 in control rats and rats with peritonitis, respectively). In conclusion, IPM distribution in intraperitoneal fluid is rapid and complete both in control rats and in rats with peritonitis.
5-Nitroimidazole Drugs Effective against Metronidazole-Resistant
Trichomonas vaginalis
and
Giardia duodenalis
Authors: Upcroft Jacqueline A. , Dunn Linda A. , Wright Janelle M. , Benakli Kamel , Upcroft Peter , Vanelle Patrice 
Published: December 2005

ABSTRACT

Metronidazole (Mz)-resistant
Giardia
and
Trichomonas
were inhibited by 1 of 30 new 5-nitroimidazole drugs. Another five drugs were effective against some but not all of the Mz-resistant parasites. This study provides the incentive for the continued design of 5-nitroimidazole drugs to bypass cross-resistance among established 5-nitromidazole antiparasitic drugs.
The K101P and K103R/V179D Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confer Resistance to Nonnucleoside Reverse Transcriptase Inhibitors
Authors: Parkin Neil T. , Gupta Soumi , Chappey Colombe , Petropoulos Christos J. 
Published: December 2005

ABSTRACTGenotypic patterns associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in the absence of well-characterized resistance mutations were identified using a database (n> 47,000) of phenotype-genotype data. Among samples with no known NNRTI mutations, the most resistant samples contained K101P (n= 35) or a combination of K103R and V179D (n= 41). Site-directed mutagenesis confirmed the importance of these mutations.
bla
IMP-9
and Its Association with Large Plasmids Carried by
Pseudomonas aeruginosa
Isolates from the People's Republic of China
Authors: Xiong Jianhui , Hynes Michael F. , Ye Huifen , Chen Huiling , Yang Yinmei , M'Zali Fatima , Hawkey Peter M. 
Published: December 2005

ABSTRACT

A novel plasmid-mediated metallo-β-lactamase (IMP-9) is described in seven isolates of
Pseudomonas aeruginosa
from Guangzhou, China, isolated in 2000. The gene was carried on a large (∼450-kb) IncP-2 conjugative plasmid. This is the first report of carriage of
bla
IMP
genes on such large plasmids.
Lethal Action of Quinolones against a Temperature-Sensitive
dnaB
Replication Mutant of
Escherichia coli
Authors: Zhao Xilin , Malik Muhammad , Chan Nymph , Drlica-Wagner Alex , Wang Jian-Ying , Li Xinying , Drlica Karl 
Published: December 2005

ABSTRACT

Inhibition of DNA replication in an
Escherichia coli dnaB-22
mutant failed to block quinolone-mediated lethality. Inhibition of protein synthesis by chloramphenicol inhibited nalidixic acid lethality and, to a lesser extent, ciprofloxacin lethality in both
dnaB-22
and wild-type cells. Thus, major features of quinolone-mediated lethality do not depend on ongoing replication.
Norfloxacin Blood-Brain Barrier Transport in Rats Is Not Affected by Probenecid Coadministration
Authors: Marchand Sandrine , Forsell Anna , Chenel Marylore , Comets Emmanuelle , Lamarche Isabelle , Couet William 
Published: December 2005

ABSTRACTThe effect of probenecid (PRO) on norfloxacin (NOR) blood-brain barrier transport was investigated with rats by microdialysis. Maximum brain drug concentrations were rapidly attained, and the brain penetration factor was close to 5% in the absence and presence of PRO. In conclusion, PRO has no effect on NOR blood-brain barrier transport.
Multicenter Antimicrobial Susceptibility Survey of Gram-Negative Bacteria Isolated from Patients with Community-Acquired Infections in the People's Republic of China
Authors: Ling Thomas K. W. , Xiong Jianhui , Yu Yunsong , Lee Ching Ching , Ye Huifen , Hawkey Peter M. 
Published: December 2005

ABSTRACT

A survey of 2,099 gram-negative bacilli from community infections at seven centers in the People's Republic of China is reported. The rates of resistance of 1,615 isolates of the family
Enterobacteriaceae
were as follows: 40.8% for ciprofloxacin, 32.2% for gentamicin, 0% for imipenem or ertapenem, and 14.7% for cefotaxime. The rates of extended-spectrum β-lactamase production were 16% for
Escherichia coli
and 17% for
Klebsiella
.
Comparative In Vitro Activities of Retapamulin (SB-275833) against 141 Clinical Isolates of
Propionibacterium
spp., Including 117
P. acnes
Isolates
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi A. , Tyrrell Kerin L. , Fernandez Helen T. 
Published: December 2005

ABSTRACT

Using the NCCLS agar dilution method, we studied the in vitro activity of retapamulin (SB-275833) against 141 clinical isolates of
Propionibacterium
species, including seven multiresistant strains, and found retapamulin to be the most active agent among those tested with MICs of ≤1 μg/ml against all isolates.
Ciprofloxacin-Resistant
Salmonella enterica
Serovar Typhimurium Strains Are Difficult To Select in the Absence of AcrB and TolC
Authors: Ricci Vito , Tzakas Peter , Buckley Anthony , Coldham Nick C. , Piddock Laura J. V. 
Published: December 2005

ABSTRACT

It has been proposed that lack of a functional efflux system(s) will lead to a lower frequency of selection of resistance to fluoroquinolones and other antibiotics. We constructed five strains of
Salmonella enterica
serovar Typhimurium SL1344 that lacked efflux gene components of resistance nodulation cell division pumps (
acrB
,
acrD
,
acrF
,
acrBacrF
, and
tolC
) plus three strains that lack genes that effect efflux gene expression (
marA
,
soxS
, and
ramA
) and a hypermutable strain (
mutS
::
aph
). Strains were exposed to ciprofloxacin at 2× the MIC in agar, in the presence and absence of Phe-Arg-β-naphthylamide, an efflux pump inhibitor. Mutants were selected from all strains except those lacking
acrB
,
tolC
, or
acrBacrF
. For strains from which mutants were selected, there were no significant differences between the frequencies of resistance. Except for mutants of the
ramA
::
aph
strain, two phenotypes arose: resistance to quinolones only and multiple antibiotic resistance (MAR).
ramA
::
aph
mutants were resistant to quinolones only, suggesting a role for
ramA
in MAR in
S. enterica
serovar Typhimurium. Phe-Arg-β-naphthylamide (20 μg/ml) had no effect on the frequencies of resistance or ciprofloxacin MICs. In conclusion, functional AcrB and TolC in
S. enterica
serovar Typhimurium are important for the selection of ciprofloxacin-resistant mutants.
Arginine or Nitrate Enhances Antibiotic Susceptibility of
Pseudomonas aeruginosa
in Biofilms
Authors: Borriello Giorgia , Richards Lee , Ehrlich Garth D. , Stewart Philip S. 
Published: December 2005

ABSTRACT

Arginine enhanced the killing of
Pseudomonas aeruginosa
by ciprofloxacin and tobramycin under anaerobic, but not aerobic, growth conditions. Arginine or nitrate also enhanced the killing by these antibiotics in mature biofilms, reducing viable cell counts by a factor of 10 to 100 beyond that achieved by antibiotics alone.
Different Modes of Action of Naphthyridones in Gram-Positive and Gram-Negative Bacteria
Authors: Buurman Ed T. , Johnson Kenneth D. , Kelly Roxanne K. , MacCormack Kathy 
Published: December 2005

ABSTRACT

Naphthyridones that were recently described as a class of translation inhibitors in gram-positive bacteria mediate their mode of action via GyrA in
Haemophilus influenzae
and
Escherichia coli
. These are the first examples of compounds in which modes of action in different bacterial pathogens are mediated through widely different targets.
Bloodstream Infections with Metallo-β-Lactamase-Producing
Pseudomonas aeruginosa
: Epidemiology, Microbiology, and Clinical Outcomes
Authors: Marra Alexandre R. , Pereira Carlos Alberto P. , Gales Ana Cristina , Menezes Liana C. , Cal Ruy Guilherme R. , de Souza José Marconi A. , Edmond Michael B. , Faro Cynthia , Wey Sérgio B. 
Published: December 2005

ABSTRACT

Pseudomonas aeruginosa
strains that produce metallo-β-lactamases (MBLs) are becoming increasingly prevalent. We evaluated the epidemiological and microbiological characteristics of monomicrobial bloodstream infections caused by MBL-producing
P. aeruginosa
isolates, as well as the clinical outcomes in patients with these infections.
Dexamethasone Attenuates Staphylococcal Enterotoxin B-Induced Hypothermic Response and Protects Mice from Superantigen-Induced Toxic Shock
Authors: Krakauer Teresa , Buckley Marilyn 
Published: December 2005

ABSTRACTThe superantigenic staphylococcal enterotoxins are important virulence factors and contribute to various diseases, including food poisoning and toxic shock. Dexamethasone, an anti-inflammatory agent, attenuated staphylococcal enterotoxin B (SEB)-induced hypothermia and serum proinflammatory cytokines and improved survival from 0% to 86% in a lethal mouse model of SEB-mediated shock.
Rifampin Augments Cytokine-Induced Nitric Oxide Production in Human Alveolar Epithelial Cells
Authors: Yuhas Yael , Berent Eva , Ovadiah Hila , Azoulay Inbar , Ashkenazi Shai 
Published: December 2005

ABSTRACT

Rifampin increased nitric oxide production and inducible nitric oxide synthase expression in alveolar cells stimulated with cytokines. Nitric oxide concentrations after induction with cytokines, cytokines with 10 μg/ml rifampin, and cytokines with 50 μg/ml rifampin were 3.2, 4.5, and 8.8 μM, respectively (
P
< 0.02 versus cytokines alone). This indicates that rifampin modulates the immune response.
Multidrug-Resistant
Pseudomonas aeruginosa
: Risk Factors and Clinical Impact
Authors: Aloush Valerie , Navon-Venezia Shiri , Seigman-Igra Yardena , Cabili Shaltiel , Carmeli Yehuda 
Published: December 2005

ABSTRACT

Pseudomonas aeruginosa
, a leading nosocomial pathogen, may become multidrug resistant (MDR). Its rate of occurrence, the individual risk factors among affected patients, and the clinical impact of infection are undetermined. We conducted an epidemiologic evaluation and molecular typing using pulsed-field gel electrophoresis (PFGE) of 36 isolates for 82 patients with MDR
P. aeruginosa
and 82 controls matched by ward, length of hospital stay, and calendar time. A matched case-control study identified individual risk factors for having MDR
P. aeruginosa
, and a retrospective matched-cohort study examined clinical outcomes of such infections. The 36 isolates belonged to 12 PFGE clones. Two clones dominated, with one originating in an intensive care unit (ICU). Cases and controls had similar demographic characteristics and numbers of comorbid conditions. A multivariate model identified ICU stay, being bedridden, having high invasive devices scores, and being treated with broad-spectrum cephalosporins and with aminoglycosides as significant risk factors for isolating MDR
P. aeruginosa
. Having a malignant disease was a protective factor (odds ratio [OR] = 0.2;
P
= 0.03). MDR
P. aeruginosa
was associated with severe outcomes compared to controls, including increased mortality (OR = 4.4;
P
= 0.04), hospital stay (hazard ratio, 2;
P
= 0.001), and requirement for procedures (OR = 5.4;
P
= 0.001). The survivors functioned more poorly at discharge than the controls, and more of the survivors were discharged to rehabilitation centers or chronic care facilities. The epidemiology of MDR
P. aeruginosa
is complex. Critically ill patients that require intensive care and are treated with multiple antibiotic agents are at high risk. MDR
P. aeruginosa
infections are associated with severe adverse clinical outcomes.
High Prevalence of Antimicrobial Resistance among
Shigella
Isolates in the United States Tested by the National Antimicrobial Resistance Monitoring System from 1999 to 2002
Authors: Sivapalasingam Sumathi , Nelson Jennifer M. , Joyce Kevin , Hoekstra Mike , Angulo Frederick J. , Mintz Eric D. 
Published: December 2005

ABSTRACT

Shigella
spp. infect approximately 450,000 persons annually in the United States, resulting in over 6,000 hospitalizations. Since 1999, the National Antimicrobial Resistance Monitoring System (NARMS) for Enteric Bacteria has tested every 10th
Shigella
isolate from 16 state or local public health laboratories for susceptibility to 15 antimicrobial agents. From 1999 to 2002, NARMS tested 1,604 isolates. Among 1,598 isolates identified to species level, 1,278 (80%) were
Shigella sonnei
, 295 (18%) were
Shigella flexneri
, 18 (1%) were
Shigella boydii
, and 7 (0.4%) were
Shigella dysenteriae
. Overall, 1,251 (78%) were resistant to ampicillin and 744 (46%) were resistant to trimethoprim-sulfamethoxazole (TMP-SMX). Prevalence of TMP-SMX- or ampicillin- and TMP-SMX-resistant
Shigella sonnei
isolates varied by geographic region, with lower rates in the South and Midwest regions (TMP-SMX resistance, 27% and 30%, respectively; ampicillin and TMP-SMX resistance, 25% and 22%, respectively) and higher rates in the East and West regions (TMP-SMX resistance, 66% and 80%, respectively; ampicillin and TMP-SMX resistance, 54% and 65%, respectively). Nineteen isolates (1%) were resistant to nalidixic acid (1% of
S. sonnei
and 2% of
S. flexneri
isolates); 12 (63%) of these isolates had decreased susceptibility to ciprofloxacin. One
S. flexneri
isolate was resistant to ciprofloxacin. All isolates were susceptible to ceftriaxone. Since 1986, resistance to ampicillin and TMP-SMX has dramatically increased.
Shigella
isolates in the United States remain susceptible to ciprofloxacin and ceftriaxone.
Multiple Combination Bactericidal Testing of Staphylococcal Biofilms from Implant-Associated Infections
Authors: Saginur Raphael , StDenis Melissa , Ferris Wendy , Aaron Shawn D. , Chan Francis , Lee Craig , Ramotar Karam 
Published: December 2005

ABSTRACT

Standardized susceptibility testing fails to predict in vivo resistance of device-related infections to antimicrobials. We assessed agents and combinations of antimicrobials against clinical isolates of
Staphylococcus epidermidis
and
S. aureus
(methicillin-resistant
S. aureus
and methicillin-sensitive
S. aureus
) retrieved from device-associated infections. Isolates were grown planktonically and as biofilms. Biofilm cultures of the organisms were found to be much more resistant to inhibitory and bactericidal effects of single and combination antibiotics than planktonic cultures (
P
< 0.001). Rifampin was the most common constituent of antibiotic combinations active against staphylococcal biofilms. Other frequently effective antimicrobials were vancomycin and fusidic acid. Susceptibility testing involving biofilm-associated bacteria suggests new options for combination antibiotic therapy.
Comparison of Censored Regression and Standard Regression Analyses for Modeling Relationships between Antimicrobial Susceptibility and Patient- and Institution-Specific Variables
Authors: Hammel Jeffrey P. , Bhavnani Sujata M. , Jones Ronald N. , Forrest Alan , Ambrose Paul G. 
Published: December 2005

ABSTRACT

In order to identify patients likely to be infected with resistant bacterial pathogens, analytic methods such as standard regression (SR) may be applied to surveillance data to determine patient- and institution-specific factors predictive of an increased MIC. However, the censored nature of MIC data (e.g., MIC ≤ 0.5 mg/liter or MIC > 8 mg/liter) imposes certain limitations on the use of SR. In order to investigate the nature of these limitations, simulations were performed to compare a regression tailored for censored data (censored regression [CR]) and one tailored for an SR. By using a model relating piperacillin-tazobactam MICs against
Enterobacter
spp. to patient age and hospital bed capacity, 200 simulations of 500 isolates were performed. Various MIC censoring patterns were imposed by using 26 left- or right-censored (
L
,
R
) pairs (i.e., MICs ≤ 2 mg/liter

L

[2

L

] or MICs > 2 mg/liter

R

[2

R

], respectively). Data were fit by CR and SR for which censored MICs were either (i) excluded, (ii) replaced by 2

L

or 2

R

, or (iii) replaced by 2

L
− 1

or 2

R
+ 1

. Total censoring for the 26 pairs ranged from 7 to 86%. By CR, deviations of average parameter estimates from the true parameter values were <0.10 log
2
(mg/liter) for all parameters for each of the 26 pairs. By SR, these deviations were >0.10 log
2
(mg/liter) for at least 18 of the 26 pairs for all but one parameter. Two-standard-error confidence intervals for individual parameters contained as little as 0% of cases for all SR approaches but ≥91.5% of cases for the CR approach. When censored MIC data are modeled, CR may reduce or eliminate biased parameter estimates obtained by SR.