bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial Susceptibility of Invasive
Streptococcus pneumoniae
Isolates in Portugal over an 11-Year Period
Authors: Dias Ricardo , Louro Deolinda ,   the Antimicrobial Resistance Surveillance Program in Portugal, Caniça Manuela 
Published: May 2006

ABSTRACT

This national surveillance study presents the in vitro activities of the main antimicrobial agents against 1,331
S. pneumoniae
isolates as tested by an agar dilution method according to the guidelines of the Clinical and Laboratory Standards Institute (formerly NCCLS). The strains were isolated in several regions of Portugal from cases of invasive disease over an 11-year period (1994 to 2004). This study shows that the percentage of penicillin-nonsusceptible strains increased from 12% in 1994 to 28.5% in 2000. Then the rate declined to 17.7% in 2003 but increased again to 23.2% in 2004. Nevertheless, the rate of highly resistant isolates declined consistently, to 0.9% in 2001 to 2004. Ceftriaxone- and cefotaxime-nonsusceptible isolates became less frequent, from 4% and 8%, respectively, in 1994 to ≤1% in 2004. The macrolide-lincosamide-streptogramin B phenotype was the predominant macrolide phenotype found. The increase in the percentage of isolates that were only nonsusceptible to erythromycin (3.7% in 1994 to 1998 to 9.1% in 2002 to 2004) was similar to that for isolates with coresistance to penicillin and erythromycin (3.3% in 1994 to 1998 to 9.1% in 2002 to 2004). The nonsusceptibility to ciprofloxacin increased during recent years, from 0.5% in 2002 to 3.5% in 2004. Multidrug resistance also increased in recent years: from 7.9% in 2002 to 15.6% in 2004. The increasing use of macrolides could be causing the increase in penicillin and multidrug resistance, due to the coresistance to macrolides. The use of penicillin to treat empirical invasive pneumococci infections may need to be reconsidered.
Comparative Efficacies, Toxicities, and Tissue Concentrations of Amphotericin B Lipid Formulations in a Murine Pulmonary Aspergillosis Model
Authors: Olson Jon A. , Adler-Moore Jill P. , Schwartz Julie , Jensen Gerard M. , Proffitt Richard T. 
Published: May 2006

ABSTRACT

Invasive aspergillosis, an important cause of morbidity and mortality in immunosuppressed (IS) patients, is often treated with amphotericin B lipid formulations. In the present study, liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) were compared in treatment of murine pulmonary aspergillosis. Uninfected, IS mice were treated for 4 days with 1, 4, 8, or 12 mg L-AMB or ABLC/kg of body weight, and their lungs were analyzed by high-performance liquid chromatography for drug concentrations. IS mice intranasally challenged with
Aspergillus fumigatus
were treated with 12, 15, or 20 mg/kg L-AMB or ABLC and monitored for survival, fungal burden (CFU), and tissue drug concentration. Blood urea nitrogen (BUN) levels and kidney histopathology were determined for uninfected and infected mice given 15 or 20 mg/kg L-AMB or ABLC. The results showed that both drugs had therapeutic levels of drug (>3.0 μg/g) in the lungs of uninfected or infected mice, and 24 h after the last dose, ABLC levels were significantly higher than L-AMB levels (
P
< 0.02). L-AMB and ABLC at 12 mg/kg both produced 57% survival, but only L-AMB at 15 or 20 mg/kg further increased survival to 80 to 90%, with BUN levels and kidney morphology similar to those of controls. Survival at 15 or 20 mg/kg ABLC was not significantly different than that of controls, and BUN levels were significantly elevated, with tubular alterations in uninfected animals and acute necrosis in kidney tubules of infected animals. In conclusion, although both drugs were effective in prolonging survival at 12 mg/kg, the reduced nephrotoxicity of L-AMB increased its therapeutic index, allowing for its safe and effective use at 15 or 20 mg/kg.
Clinical Correlation of the CLSI Susceptibility Breakpoint for Piperacillin- Tazobactam against Extended-Spectrum-β-Lactamase-Producing
Escherichia coli
and
Klebsiella
Species
Authors: Gavin Patrick J. , Suseno Mira T. , Thomson Richard B. , Gaydos J. Michael , Pierson Carl L. , Halstead Diane C. , Aslanzadeh Jaber , Brecher Stephen , Rotstein Coleman , Brossette Stephen E. , Peterson Lance R. 
Published: May 2006

ABSTRACT

We assessed infections caused by extended-spectrum-β-lactamase-producing
Escherichia coli
or
Klebsiella
spp. treated with piperacillin-tazobactam to determine if the susceptibility breakpoint predicts outcome. Treatment was successful in 10 of 11 nonurinary infections from susceptible strains and in 2 of 6 infections with MICs of >16/4 μg/ml. All six urinary infections responded to treatment regardless of susceptibility.
Synergistic In Vitro Antiretroviral Activity of a Humanized Monoclonal Anti-CD4 Antibody (TNX-355) and Enfuvirtide (T-20)
Authors: Zhang Xing-Quan , Sorensen Meredith , Fung Michael , Schooley Robert T. 
Published: May 2006

ABSTRACTRecently, antiretroviral agents directed at several steps involved in viral entry have been shown to reduce viral replication in vitro and in vivo. We have demonstrated a high level of in vitro synergistic antiretroviral activity for two entry inhibitors that are directed at sequential steps in the entry process.
Using Interrupted Time Series Analysis To Assess Associations of Fluoroquinolone Formulary Changes with Susceptibility of Gram-Negative Pathogens and Isolation Rates of Methicillin-Resistant
Staphylococcus aureus
Authors: Bosso John A. , Mauldin Patrick D. 
Published: May 2006

ABSTRACT

The use of fluoroquinolones has been linked to increasing bacterial resistance and infection and/or colonization with already resistant pathogens both as a risk factor and based on volume of use. Changes in individual fluoroquinolones used in an institution may also be related to these clinical problems. Interrupted time series analysis, which allows for assessment of the associations of an outcome attributable to a specific event in time, was used to study the effect of changes in our hospital's fluoroquinolone formulary on fluoroquinolone susceptibility rates in select gram-negative pathogens and the methicillin-resistant
Staphylococcus aureus
(MRSA) isolation rate. Susceptibility rates to ciprofloxacin were considered for the period of 1993 through 2004, while the MRSA isolation rate was assessed from 1995 through 2004. Levofloxacin was added to the formulary in 1999, and gatifloxacin was substituted for levofloxacin in 2001. Statistically significant changes in the already declining rates of susceptibility of
Pseudomonas aeruginosa
(
P
, 0.042) and
Escherichia coli
(
P
, 0.004) to ciprofloxacin and in the already rising MRSA isolation rate (
P
, 0.001) were associated with the addition of levofloxacin to the formulary. Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in
E. coli
susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate. No associations were detected on susceptibility of
Klebsiella pneumoniae
or
Proteus mirabilis
to ciprofloxacin. These findings suggest that potential changes in susceptibility to fluoroquinolones and isolation of MRSA may vary by both drug and organism.
In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone
Authors: Park Hee-Soo , Kim Hyun-Joo , Seol Min-Jung , Choi Dong-Rack , Choi Eung-Chil , Kwak Jin-Hwan 
Published: May 2006

ABSTRACT
DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.
Inhibition of Mammalian Mitochondrial Protein Synthesis by Oxazolidinones
Authors: McKee E. E. , Ferguson M. , Bentley A. T. , Marks T. A. 
Published: May 2006

ABSTRACTThe effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.
Impact of Human Immunodeficiency Virus Type 1 Subtype C on Drug Resistance Mutations in Patients from Botswana Failing a Nelfinavir-Containing Regimen
Authors: Doualla-Bell Florence , Avalos Ava , Gaolathe Tendani , Mine Madisa , Gaseitsiwe Simani , Ndwapi Ndwapi , Novitsky Vladimir A. , Brenner Bluma , Oliveira Maureen , Moisi Daniella , Moffat Howard , Thior Ibou , Essex Max , Wainberg Mark A. 
Published: May 2006

ABSTRACT
Among 16 human immunodeficiency virus-infected (subtype C) Batswana patients who failed nelfinavir (NFV)-containing regimens, the most prevalent mutation observed was D30N (54%), followed by L90M (31%). L89I, K20T/I, and E35D polymorphic changes were also identified. These findings suggest that subtype C viruses in Botswana may develop resistance to NFV via subtype-specific pathways.
Model System To Evaluate the Effect ofampDMutations on AmpC-Mediated β-Lactam Resistance
Authors: Schmidtke Amber J. , Hanson Nancy D. 
Published: May 2006

ABSTRACTMutations within the structural gene ofampDcan lead to AmpC overproduction and increases in β-lactam MICs in organisms with an inducibleampC. However, identification of mutations alone cannot predict the impact that those mutations have on AmpD function. Therefore, a model system was designed to determine the effect ofampDmutations on ceftazidime MICs using an AmpD−mutantEscherichia colistrain which produced an inducible plasmid-encoded AmpC.ampDgenes were amplified by PCR from strains ofE. coli,Citrobacter freundii, andPseudomonas aeruginosa. Also, carboxy-terminal truncations ofC. freundii ampDgenes were constructed representing deletions of 10, 21, or 25 codons. AmplifiedampDproducts were cloned into pACYC184 containing inducibleblaACT-1-ampR. Plasmids were transformed intoE. colistrains JRG582 (AmpD−) and K-12 259 (AmpD+). The strains were evaluated for a derepressed phenotype using ceftazidime MICs. Some mutatedampDgenes, including theampDgene of a derepressedC. freundiiisolate, resulted in substantial decreases in ceftazidime MICs (from >256 μg/ml to 12 to 24 μg/ml) for the AmpD−strain, indicating no role for these mutations in derepressed phenotypes. However,ampDtruncation products andampDfrom a partially derepressedP. aeruginosastrain resulted in ceftazidime MICs of >256 μg/ml, indicating a role for these gene modifications in derepressed phenotypes. The use of this model system indicated that alternative mechanisms were involved in the derepressed phenotype observed in strains ofC. freundiiandP. aeruginosa. The alternative mechanism involved in the derepressed phenotype of theC. freundiiisolate was downregulation ofampDtranscription.
Recombinant
Eimeria
Protozoan Protein Elicits Resistance to Acute Phlebovirus Infection in Mice but Not Hamsters
Authors: Gowen Brian B. , Smee Donald F. , Wong Min-Hui , Judge John W. , Jung Kie-Hoon , Bailey Kevin W. , Pace Anne M. , Rosenberg Barnett , Sidwell Robert W. 
Published: May 2006

ABSTRACT

A protein antigen from an
Eimeria
protozoan has recently been reported to induce antitumor activity in mice. This activity most likely results from the strong induction of interkeukin-12 (IL-12) and gamma interferon (IFN-γ), which are also essential factors in the establishment of protective immunity against viral infection. We evaluated recombinant
Eimeria
antigen (rEA) as a potential immunotherapeutic agent in mouse and hamster models of acute phleboviral disease. Punta Toro virus (PTV) was highly sensitive to a single dose of nanogram quantities of rEA in the mouse infection model. Intraperitoneal treatment with rEA also reduced virus load and liver damage associated with PTV infection. IL-12 was elicited following exposure of uninfected mice to quantities of rEA of 10 ng or greater, and the levels peaked at between 3 and 8 h postexposure. IFN-γ release was induced more slowly and required less rEA (1 ng) to produce a significant rise in systemic levels. The induction of IL-12 and IFN-γ involved in the coordination of innate and adaptive immune responses to microbial pathogens required myeloid differentiation factor 88, a signaling adaptor shared by most members of the Toll-like receptor (TLR) family. Despite encouraging results in the murine system, rEA failed to protect hamsters challenged with PTV. Our findings suggest that hamsters may lack functional TLR11, which has recently been shown to recognize a profilin-like protein homologous to rEA from the protozoan
Toxoplasma gondii
. Further investigation into the immunostimulatory capacity of rEA in other mammalian systems is necessary.
Effect of Porins and Plasmid-Mediated AmpC β-Lactamases on the Efficacy of β-Lactams in Rat Pneumonia Caused by
Klebsiella pneumoniae
Authors: Padilla Emma , Alonso Diana , Doménech-Sánchez Antonio , Gomez Cristina , Pérez José Luis , Albertí Sebastián , Borrell Nuria 
Published: May 2006

ABSTRACT

The in vivo activities of imipenem, meropenem, and cefepime were studied in a model of rat pneumonia caused by a plasmid-mediated AmpC β-lactamase ACT-1-producing
Klebsiella pneumoniae
strain (
K. pneumoniae
strain 12) and a derivative porin-deficient mutant (
K. pneumoniae
strain 12dp). No differences between these activities were seen with
K. pneumoniae
12. Only meropenem showed an activity slightly better than that of imipenem with
K. pneumoniae
12dp.
Novel Mobile Variants of Staphylococcal Cassette Chromosome
mec
in
Staphylococcus aureus
Authors: Jansen W. T. M. , Beitsma M. M. , Koeman C. J. , van Wamel W. J. B. , Verhoef J. , Fluit A. C. 
Published: May 2006

ABSTRACT

Staphylococcus aureus
staphylococcal cassette chromosome
mec
type IV (SSC
mec
IV) is associated with virulent community-acquired methicillin-resistant
Staphylococcus aureus
(MRSA) and frequent horizontal transfer among staphylococci. To gain insight into the mechanism of transfer, we studied the
ccrA/B
type 2 recombinase-mediated excision of SCC
mec
IV (
n
= 5 strains) and SCC
mec
II (
n
= 2). In SCC
mec
IV- but not SCC
mec
II-containing strains, spontaneous excision of the cassette was observed. Introduction of
ccrA/B
type 2 recombinase genes under control of an
S. aureus
bacterial phage promoter in the different strains yielded excision of SCC
mec
II and multiple excision variants of SCC
mec
IV. Sequencing of the alternatively excised products in SCC
mec
IV strains identified a 100-bp shortened SCC
mec
′ variant and a 5,877-bp, conserved SCC-like element that lacks
mecA
and
ccrA/B
recombinases. Excision of the SCC-like element in wild-type
S. aureus
was dependent on the presence of SCC
mec
. The element could be excised separately or as part of a novel composite cassette together with SCC
mec
. The relative abundance of and variety in SCC
mec
IV excisions may contribute to the frequency of horizontal transfer and genetic plasticity in SCC
mec
IV MRSA strains.
Biosynthetic Pathway for Mannopeptimycins, Lipoglycopeptide Antibiotics Active against Drug-Resistant Gram-Positive Pathogens
Authors: Magarvey Nathan A. , Haltli Brad , He Min , Greenstein Michael , Hucul John A. 
Published: May 2006

ABSTRACT

The mannopeptimycins are a novel class of lipoglycopeptide antibiotics active against multidrug-resistant pathogens with potential as clinically useful antibacterials. This report is the first to describe the biosynthesis of this novel class of mannosylated lipoglycopeptides. Included here are the cloning, sequencing, annotation, and manipulation of the mannopeptimycin biosynthetic gene cluster from
Streptomyces hygroscopicus
NRRL 30439. Encoded by genes within the mannopeptimycin biosynthetic gene cluster are enzymes responsible for the generation of the hexapeptide core (nonribosomal peptide synthetases [NRPS]) and tailoring reactions (mannosylation, isovalerylation, hydroxylation, and methylation). The NRPS system is noncanonical in that it has six modules utilizing only five amino acid-specific adenylation domains and it lacks a prototypical NRPS macrocyclizing thioesterase domain. Analysis of the mannopeptimycin gene cluster and its engineering has elucidated the mannopeptimycin biosynthetic pathway and provides the framework to make new and improved mannopeptimycins biosynthetically.
Mechanism of Enhanced Activity of Liposome-Entrapped Aminoglycosides against Resistant Strains of
Pseudomonas aeruginosa
Authors: Mugabe Clement , Halwani Majed , Azghani Ali O. , Lafrenie Robert M. , Omri Abdelwahab 
Published: May 2006

ABSTRACT

Pseudomonas aeruginosa
is inherently resistant to most conventional antibiotics. The mechanism of resistance of this bacterium is mainly associated with the low permeability of its outer membrane to these agents. We sought to assess the bactericidal efficacy of liposome-entrapped aminoglycosides against resistant clinical strains of
P. aeruginosa
and to define the mechanism of liposome-bacterium interactions. Aminoglycosides were incorporated into liposomes, and the bactericidal efficacies of both free and liposomal drugs were evaluated. To define the mechanism of liposome-bacterium interactions, transmission electron microscopy (TEM), flow cytometry, lipid mixing assay, and immunocytochemistry were employed. Encapsulation of aminoglycosides into liposomes significantly increased their antibacterial activity against the resistant strains used in this study (MICs of ≥32 versus ≤8 μg/ml). TEM observations showed that liposomes interact intimately with the outer membrane of
P. aeruginosa
, leading to the membrane deformation. The flow cytometry and lipid mixing assays confirmed liposome-bacterial membrane fusion, which increased as a function of incubation time. The maximum fusion rate was 54.3% ± 1.5% for an antibiotic-sensitive strain of
P. aeruginosa
and 57.8% ± 1.9% for a drug-resistant strain. The fusion between liposomes and
P. aeruginosa
significantly enhanced the antibiotics' penetration into the bacterial cells (3.2 ± 2.3 versus 24.2 ± 6.2 gold particles/bacterium,
P
≤ 0.001). Our data suggest that liposome-entrapped antibiotics could successfully resolve infections caused by antibiotic-resistant
P. aeruginosa
through an enhanced mechanism of drug entry into the bacterial cells.
Postgenomic Scan of Metallo-β-Lactamase Homologues in Rhizobacteria: Identification and Characterization of BJP-1, a Subclass B3 Ortholog fromBradyrhizobium japonicum
Authors: Stoczko Magdalena , Frère Jean-Marie , Rossolini Gian Maria , Docquier Jean-Denis 
Published: May 2006

ABSTRACTThe diffusion of metallo-β-lactamases (MBLs) among clinically important human pathogens represents a therapeutic issue of increasing importance. However, the origin of these resistance determinants is largely unknown, although an important number of proteins belonging to the MBL superfamily have been identified in microbial genomes. In this work, we analyzed the distribution and function of genes encoding MBL-like proteins in the classRhizobiales. Among 12 released complete genomes of members of the classRhizobiales, a total of 57 open reading frames (ORFs) were found to have the MBL conserved motif and identity scores with MBLs ranging from 8 to 40%. On the basis of the best identity scores with known MBLs, four ORFs were cloned intoEscherichia colifor heterologous expression. Among their products, one (blr6230) encoded by theBradyrhizobium japonicumUSDA110 genome, named BJP-1, hydrolyzed β-lactams when expressed inE. coli. BJP-1 enzyme is most closely related to the CAU-1 enzyme fromCaulobacter vibrioides(40% amino acid sequence identity), a member of subclass B3 MBLs. A kinetic analysis revealed that BJP-1 efficiently hydrolyzed most β-lactam substrates, except aztreonam, ticarcillin, and temocillin, with the highest catalytic efficiency measured with meropenem. Compared to other MBLs, BJP-1 was less sensitive to inactivation by chelating agents.
Diminished Macrophage Inflammatory Response to
Staphylococcus aureus
Isolates Exposed to Daptomycin versus Vancomycin or Oxacillin
Authors: English B. Keith , Maryniw Erik M. , Talati Ajay J. , Meals Elizabeth A. 
Published: May 2006

ABSTRACT

Exposure of any of six clinical isolates of
Staphylococcus aureus
to daptomycin alone or in combination with vancomycin or oxacillin (compared with vancomycin or oxacillin alone) led to a dampened macrophage inflammatory response with diminished tumor necrosis factor secretion and reduced accumulation of inducible nitric oxide synthase protein.
DNA Microarray for Detection of Macrolide Resistance Genes
Authors: Cassone Marco , D'Andrea Marco M. , Iannelli Francesco , Oggioni Marco R. , Rossolini Gian Maria , Pozzi Gianni 
Published: May 2006

ABSTRACT

A DNA microarray was developed to detect bacterial genes conferring resistance to macrolides and related antibiotics. A database containing 65 nonredundant genes selected from publicly available DNA sequences was constructed and used to design 100 oligonucleotide probes that could specifically detect and discriminate all 65 genes. Probes were spotted on a glass slide, and the array was reacted with DNA templates extracted from 20 reference strains of eight different bacterial species (
Streptococcus pneumoniae
,
Streptococcus pyogenes
,
Enterococcus faecalis
,
Enterococcus faecium
,
Staphylococcus aureus
,
Staphylococcus haemolyticus
,
Escherichia coli
, and
Bacteroides fragilis
) known to harbor 29 different macrolide resistance genes. Hybridization results showed that probes reacted with, and only with, the expected DNA templates and allowed discovery of three unexpected genes, including
msr
(SA) in
B. fragilis
, an efflux gene that has not yet been described for gram-negative bacteria.