bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Cluster of Plasmid-Located Class 1 Integrons in
Vibrio cholerae
O1 and a
dfrA15
Cassette-Containing Integron in
Vibrio parahaemolyticus
Isolated in Angola
Authors: Ceccarelli Daniela , Salvia Anna Maria , Sami Joana , Cappuccinelli Piero , Colombo Mauro Maria 
Published: June 2006

ABSTRACT

The resistance profile and its correlation with mobile genetic elements were investigated in 11
Vibrio cholerae
O1 and 2
Vibrio parahaemolyticus
clinical isolates, as well as in 1
V. cholerae
O1 and 1
V. cholerae
non-O1 environmental isolate, isolated between 1991 and 1996 in different provinces of Angola. All clinical isolates of
V. cholerae
O1 were resistant to ampicillin, chloramphenicol, trimethoprim, sulfamethoxazole, and tetracycline. They also contained a large conjugative plasmid (p3iANG) with a set of three class 1 integrons harboring
dfrA15
,
blaP1
, and
qacH-aadA8
cassettes, which code for resistance to trimethoprim, beta-lactams, quaternary ammonium compounds, and aminoglycosides, clustered in a 19-kb region. Chloramphenicol (
cat1
), kanamycin (
aph
), sulfonamide (
sul2
), and tetracycline (
tetG
) resistance genes were also carried on the plasmid within the same 19-kb region. A chromosomal integron containing the
dfrA15
cassette was also revealed in
V. parahaemolyticus
strains. SXT integrase genes were present in six
V. cholerae
isolates but apparently were not associated with known SXT-associated resistance genes. This study indicates that plasmids and integrons contributed mainly to the circulation of multiple-drug resistance determinants in
Vibrio
strains from Angola.
Detection of Influenza Viruses Resistant to Neuraminidase Inhibitors in Global Surveillance during the First 3 Years of Their Use
Authors: Monto Arnold S. , McKimm-Breschkin Jennifer L. , Macken Catherine , Hampson Alan W. , Hay Alan , Klimov Alexander , Tashiro Masato , Webster Robert G. , Aymard Michelle , Hayden Frederick G. , Zambon Maria 
Published: June 2006

ABSTRACT
Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) develops at a low level following drug treatment, and person-to-person transmission of resistant virus has not been recognized to date. The Neuraminidase Inhibitor Susceptibility Network (NISN) was established to follow susceptibility of isolates and occurrence of NAI resistance at a population level in various parts of the world. Isolates from the WHO influenza collaborating centers were screened for susceptibilities to oseltamivir and zanamivir by a chemiluminescent enzyme inhibition assay, and those considered potentially resistant were analyzed by sequence analysis of the neuraminidase genes. During the first 3 years of NAI use (1999 to 2002), 2,287 isolates were tested. Among them, eight (0.33%) viruses had a >10-fold decrease in susceptibility to oseltamivir, one (0.22%) in 1999 to 2000, three (0.36%) in 2000 to 2001, and four (0.41%) in 2001 to 2002. Six had unique changes in the neuraminidase gene compared to neuraminidases of the same subtype in the influenza sequence database. Although only one of the mutations had previously been recognized in persons receiving NAIs, none were from patients who were known to have received the drugs. During the 3 years preceding NAI use, no resistant variants were detected among 1,054 viruses. Drug use was relatively stable during the period, except for an approximate 10-fold increase in oseltamivir use in Japan during the third year. The frequency of variants with decreased sensitivity to the NAIs did not increase significantly during this period, but continued surveillance is required, especially in regions with higher NAI use.
Use of Probabilistic Modeling within a Physiologically BasedPharmacokinetic Model To Predict Sulfamethazine Residue Withdrawal Times in Edible Tissues in Swine
Authors: Buur Jennifer , Baynes Ronald , Smith Geof , Riviere Jim 
Published: June 2006

ABSTRACTThe presence of antimicrobial agents in edible tissues of food-producing animals remains a major public health concern. Probabilistic modeling techniques incorporated into a physiologically based pharmacokinetic (PBPK) model were used to predict the amounts of sulfamethazine residues in edible tissues in swine. A PBPK model for sulfamethazine in swine was adapted to include an oral dosing route. The distributions for sensitive parameters were determined and were used in a Monte Carlo analysis to predict tissue residue times. Validation of the distributions was done by comparison of the results of a Monte Carlo analysis to those obtained with an external data set from the literature and an in vivo pilot study. The model was used to predict the upper limit of the 95% confidence interval of the 99th percentile of the population, as recommended by the U.S. Food and Drug Administration (FDA). The external data set was used to calculate the withdrawal time by using the tolerance limit algorithm designed by FDA. The withdrawal times obtained by both methods were compared to the labeled withdrawal time for the same dose. The Monte Carlo method predicted a withdrawal time of 21 days, based on the amounts of residues in the kidneys. The tolerance limit method applied to the time-limited data set predicted a withdrawal time of 12 days. The existing FDA label withdrawal time is 15 days. PBPK models can incorporate probabilistic modeling techniques that make them useful for prediction of tissue residue times. These models can be used to calculate the parameters required by FDA and explore those conditions where the established withdrawal time may not be sufficient.
Activity of Retapamulin (SB-275833), a Novel Pleuromutilin, against Selected Resistant Gram-Positive Cocci
Authors: Jones Ronald N. , Fritsche Thomas R. , Sader Helio S. , Ross James E. 
Published: June 2006

ABSTRACT

Retapamulin (SB-275833), the first pleuromutilin to be developed for human topical use, was tested against a selected population of staphylococci and β-hemolytic streptococci. The MIC
90
results for retapamulin were 0.12 μg/ml for
Staphylococcus aureus
and ≤0.03 μg/ml for
Streptococcus pyogenes
; no cross-resistance was observed for organism subsets resistant to oxacillin, erythromycin, or mupirocin.
Quinolones Sensitize Gram-Negative Bacteria to Antimicrobial Peptides
Authors: Campos Miguel A. , Morey Pau , Bengoechea José A. 
Published: June 2006

ABSTRACT

The treatment of infections caused by bacteria resistant to the vast majority of antibiotics is a challenge worldwide. Antimicrobial peptides (APs) make up the front line of defense in those areas exposed to microorganisms, and there is intensive research to explore their use as new antibacterial agents. On the other hand, it is known that subinhibitory concentrations of antibiotics affect the expression of numerous bacterial traits. In this work we evaluated whether treatment of bacteria with subinhibitory concentrations of quinolones may alter the sensitivity to APs. A 1-h treatment of
Klebsiella pneumoniae
with 0.25× the MIC of ciprofloxacin rendered bacteria more sensitive to polymyxins B and E, human neutrophil defensin 1, and β-defensin 1. Levofloxacin and nalidixic acid at 0.25× the MICs also increased the sensitivity of
K. pneumoniae
to polymyxin B, whereas gentamicin and ceftazidime at 0.25× the MICs did not have such an effect. Ciprofloxacin also increased the sensitivities of
K. pneumoniae
ciprofloxacin-resistant strains to polymyxin B. Two other pathogens,
Pseudomonas aeruginosa
and
Haemophilus influenzae
, also became more sensitive to polymyxins B and E after treatment with 0.25× the MIC of ciprofloxacin. Incubation with ciprofloxacin did not alter the expression of the
K. pneumoniae
loci involved in resistance to APs. A 1-
N
-phenyl-naphthylamine assay showed that ciprofloxacin and levofloxacin increased the permeabilities of the
K. pneumoniae
and
P. aeruginosa
outer membranes, while divalent cations antagonized this action. Finally, we demonstrated that ciprofloxacin and levofloxacin increased the binding of APs to the outer membrane by using dansylated polymyxin B.
Pharmacokinetics of Unbound Linezolid in Plasma and Tissue Interstitium of Critically Ill Patients after Multiple Dosing Using Microdialysis
Authors: Buerger Cornelia , Plock Nele , Dehghanyar Pejman , Joukhadar Christian , Kloft Charlotte 
Published: June 2006

ABSTRACTThe antimicrobial agent linezolid is approved for the treatment of severe infections caused by, e.g., methicillin-resistantStaphylococcusstrains. In order to evaluate the penetration of linezolid into the interstitial space fluid (ISF) of subcutaneous adipose tissue and skeletal muscle of the target population, a microdialysis study was performed with 12 patients with sepsis or septic shock after multiple intravenous infusions. Unbound linezolid concentrations were determined for plasma and microdialysates by use of a validated high-performance liquid chromatography method. Individual compartmental pharmacokinetic (PK) analysis was performed using WinNonlin. In vivo microdialysis was found to be feasible for the determination of unbound linezolid concentrations at steady state in the ISF of critically ill patients. On average, linezolid showed good distribution into ISF but with high interindividual variability. A two-compartment model was fitted to unbound concentrations in plasma with a geometric mean distribution volume of 62.9 liters and a mean clearance of 9.18 liters/h at steady state. However, disposition characteristics changed intraindividually within the time course. In addition, an integrated model for simultaneous prediction of concentrations in all matrices was developed and revealed similar results. Based on the model-predicted unbound concentrations in ISF, a scheme of more-frequent daily dosing of linezolid for some critically ill patients might be taken into consideration to avoid subinhibitory unbound concentrations in the infected tissue. The developed integrated model will be a valuable basis for further PK data analysis to explore refined dosing guidelines that achieve effective antimicrobial therapy in all patients by use of the population PK approach.
Proteolytic Degradation of Human Antimicrobial Peptide LL-37 by
Bacillus anthracis
May Contribute to Virulence
Authors: Thwaite Joanne E. , Hibbs Stephen , Titball Richard W. , Atkins Timothy P. 
Published: June 2006

ABSTRACT

In this paper we report on the susceptibilities of a range of
Bacillus
species to the human antimicrobial peptide LL-37.
B. subtilis
showed a low level of resistance to killing by LL-37 (50% growth-inhibitory concentration [GI
50
], 1 μg/ml).
B. cereus
and
B. thuringiensis
showed intermediate levels of resistance to killing (GI
50
s, 33 μg/ml and 37 μg/ml, respectively).
B. anthracis
showed the highest level of resistance (GI
50
s, 40 to 66 μg/ml). The degradation of LL-37 by
B. anthracis
culture supernatant was blocked by the metalloprotease inhibitors EDTA and 1,10-phenanthroline, and the gene encoding the protease responsible for LL-37 degradation was not plasmid borne. Our findings suggest that alongside the classical plasmid-based virulence determinants, extracellular metalloproteases of
B. anthracis
may play a role in survival in the host.
Activities of Alkoxyalkyl Esters of Cidofovir (CDV), Cyclic CDV, and (
S
)-9-(3-Hydroxy-2-Phosphonylmethoxypropyl)Adenine against Orthopoxviruses in Cell Monolayers and in Organotypic Cultures
Authors: Lebeau Ilya , Andrei Graciela , Dal Pozzo Fabiana , Beadle James R. , Hostetler Karl Y. , De Clercq Erik , van den Oord Joost , Snoeck Robert 
Published: June 2006

ABSTRACT

The potencies of several alkoxyalkyl esters of acyclic nucleoside phosphonates against vaccinia virus and cowpox virus were evaluated in cell monolayers and three-dimensional epithelial raft cultures. Prodrugs were at least 20-fold more active than their parent compounds. Octadecycloxyethyl-(
S
)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine emerged as the most potent derivative.
Daptomycin Bactericidal Activity and Correlation between Disk and Broth Microdilution Method Results in Testing of
Staphylococcus aureus
Strains with Decreased Susceptibility to Vancomycin
Authors: Sader Helio S. , Fritsche Thomas R. , Jones Ronald N. 
Published: June 2006

ABSTRACT

A total of 207
Staphylococcus aureus
strains, including 105 well-characterized strains with decreased susceptibility to vancomycin (17 vancomycin-intermediate
S. aureus
[VISA] and 88 heteroresistant VISA [hVISA] strains) and 102 wild-type methicillin-resistant
S. aureus
(MRSA-WT) strains were tested by reference/standardized broth microdilution and disk diffusion methods, as well as by Etest (AB BIODISK, Solna, Sweden), against daptomycin and vancomycin. The lowest concentration of antimicrobial agent that killed ≥99.9% of the initial inoculum was defined as the minimum bactericidal concentration (MBC) endpoint, and time-kill curves were performed in selected strains to further evaluate bactericidal activity. All MRSA-WT and hVISA strains were inhibited by ≤1 μg/ml of daptomycin, while the VISA strains showed slightly higher daptomycin MICs (range, 0.5 to 4 μg/ml). All daptomycin MBC results were at the MIC or twofold higher. In contrast, 14.7% of MRSA-WT, 69.3% of hVISA, and all VISA strains showed a vancomycin MBC/MIC ratio of ≥32 or an MBC of ≥16 μg/ml (tolerant). The correlation coefficients between broth microdilution and disk diffusion method results were low for daptomycin (0.07) and vancomycin (0.11). Eight (3.8%) strains (all hVISA or VISA) were “nonsusceptible” to daptomycin by broth microdilution methods but susceptible by the disk diffusion method. For vancomycin, 35 (16.9%) strains were nonsusceptible by broth microdilution methods but susceptible by disk diffusion methods. In conclusion, daptomycin was highly bactericidal against
S. aureus
strains, and its bactericidal activity was not affected by decreased susceptibility to vancomycin. In contrast, many (one in seven) contemporary MRSA-WT, the majority of hVISA, and all VISA strains showed vancomycin MBC/MIC ratios consistent with tolerance, a predictor of poor clinical response. Disk diffusion tests generally failed to detect strains categorized as nonsusceptible to daptomycin or vancomycin by the reference broth microdilution method or Etest, and reassessment of breakpoints should be immediately attempted for MIC methods suggested as the test of choice.
Naturally Occurring Extended-Spectrum Cephalosporinases in
Escherichia coli
Authors: Mammeri Hedi , Poirel Laurent , Fortineau Nicolas , Nordmann Patrice 
Published: June 2006

ABSTRACT

Genetic and functional characterization of the cephalosporinases produced by 65 clonally unrelated clinical
Escherichia coli
isolates revealed genetic diversity of the
ampC
genes and showed that Gln287, Cys287, Pro296, Leu298, and Phe350 substitutions were involved in extension of the hydrolysis spectrum to include ceftazidime and cefepime.
CMT-Type β-Lactamase TEM-125, an Emerging Problem for Extended-Spectrum β-Lactamase Detection
Authors: Robin Frédéric , Delmas Julien , Archambaud Maryse , Schweitzer Cédric , Chanal Catherine , Bonnet Richard 
Published: June 2006

ABSTRACT

The clinical strain
Escherichia coli
TO799 was resistant to penicillin-clavulanate combinations and ceftazidime and was not reproducibly detected as an extended-spectrum β-lactamase (ESBL) according to the standards of the Clinical Laboratory Standards Institute (CLSI; formerly NCCLS) and the national guidelines of the French Society for Microbiology (Comité de l'Antibiogramme de la Société Française de Microbiologie). A novel β-lactamase, designated TEM-125, was responsible for this phenotype. TEM-125 harbors a complex association of mutations previously described in the ESBL TEM-12 and in the inhibitor-resistant β-lactamase TEM-39. TEM-125 is the first complex mutant TEM to present hydrolytic activity against ceftazidime (
k
cat
, 3.7 s
−1
) together with a high level of resistance to clavulanate (50% inhibitory concentration, 13.6 μM). The discovery of such an ESBL, which is difficult to detect by the usual ESBL detection methods, confirms the emergence of a complex mutant TEM subgroup and highlights the need to evaluate detection methods so as to avoid possible therapeutic failures.
Reverse Engineering Antibiotic Sensitivity in a Multidrug-Resistant
Pseudomonas aeruginosa
Isolate
Authors: Struble Julie M. , Gill Ryan T. 
Published: June 2006

ABSTRACT

Antibiotic resistance is a pervasive and growing clinical problem. We describe an evaluation of a reverse engineering approach for identifying cellular mechanisms and genes that could be manipulated to increase antibiotic sensitivity in a resistant
Pseudomonas aeruginosa
isolate. We began by chemically mutating a broadly resistant isolate of
P. aeruginosa
and screening for mutants with increased sensitivity to the aminoglycoside amikacin, followed by performing whole-genome transcriptional profiling of the mutant and wild-type strains to characterize the global changes occurring as a result of the mutations. We then performed a series of assays to characterize the mechanisms involved in the increased sensitivity of the mutant strains. We report four primary results: (i) mutations that increase sensitivity occur at a high frequency (10
−2
) relative to the frequency of those that increase resistance (10
−5
to 10
−10
) and occur at a frequency 10
4
higher than the frequency of a single point mutation; (ii) transcriptional profiles were altered in sensitive mutants, resulting in overall expression patterns more similar to those of the sensitive laboratory strain PAO1 than those of the parental resistant strain; (iii) genes found from transcriptional profiling had the more dramatic changes in expression-encoded functions related to cellular membrane permeability and aminoglycoside modification, both of which are known aminoglycoside resistance mechanisms; and finally, (iv) even though we did not identify the specific sites of mutation, several different follow-up MIC assays suggested that the mutations responsible for increased sensitivity differed between sensitive mutants.
Accelerated Denaturation of Hemoglobin and the Antimalarial Action of Chloroquine
Authors: Fitch Coy D. , Russell Natrice V. 
Published: June 2006

ABSTRACT
To study the antimalarial action of chloroquine, normal mouse erythrocytes were used as surrogates for erythrocytoid bodies. These bodies form in the endosomes of intraerythrocytic malaria parasites as they feed on their host and consist of erythrocyte cytoplasm enclosed in a vestige of the erythrocyte membrane. In suspensions of normal erythrocytes or lysates (equivalent to 5 μl of erythrocytes per ml in each case), hemoglobin underwent denaturation when it was incubated at 38°C in 150 mM sodium acetate (pH 5). It is reasonable to assume that the same phenomenon occurs in acidic endosomes. Addition of 100 μM chloroquine to the incubation mixture caused the rate of hemoglobin denaturation to double to 40 nanomoles per hour per ml of packed erythrocytes. This effect required the presence of erythrocyte stroma and was inhibited by reducing the temperature to 24°C or increasing the pH to 6. We propose that the primary antimalarial action of chloroquine is to bind to ferriprotoporphyrin IX (FP) and remove it from oxidized hemoglobin, thus producing toxic FP-chloroquine complexes and an excess of denatured globin. Furthermore, we suggest that these substances inhibit endosomal maturation and thereby cause hemoglobin accumulation in immature endosomes and masking of the lipids needed for FP dimerization. The term “masking” is used to signify that unsaturated lipids are present in parasitized erythrocytes but are specifically unavailable to promote FP dimerization.
Attock Refinery Upgradation Project
Authors: Nawaz Tariq Ahmed , Iqbal Rana Arif 
Published: June 2006

This case is about a major expansion and upgradation project undertaken at a refinery in Northern Pakistan in the 1990s. The project was the biggest expansion project since the company's inception in the 1920s. The project was carried out by a Japanese contractor, and was marked by changes in CEO's and Project Managers. Despite the vicissitudes in relationships between the construction team and company management, the project was completed in time and within budget. The case looks at project management from the client's perspective. It can be used in a module on Project Termination, or Project Monitoring and Control in a course on Project Management). The case highlights the importance of project planning, and monitoring; the management of inter-personal relationships; and 'post-mortem' analysis and learning from projects.
Gurgaon Branch
Authors: Panda Abinash , Gupta Rajen K. , Kalra Satish K. 
Published: June 2006

Gurgaon Branch was a branch of a leading public sector bank in India. Though the bank was financially sound, there seemed to be a leadership crisis in this branch. The aggregate deposit had been consistently falling over the past three years. The branch had not been able to disburse fresh advances or recover outstanding advances. Moreover, the employees were unhappy with both the branch head and the accountant. This case is concerned with transforming the culture of a public sector bank's branch that has been plagued with officers-staff conflict, inter-union rivalry and bureaucratic culture and consequently, poor financial performance, weak customer orientation and poor customers' satisfaction. This case provides a useful basis for discussing the issues and challenges involved in the process of transforming highly politicized culture to a desirable team-oriented customer-centric performing culture.
Measures of the Therapeutic Relationship in Severe Psychotic Illness: A Comparison of Two Scales
Authors: Bale Rob , Catty Jocelyn , Watt Hilary , Greenwood Nan , Burns Tom 
Published: June 2006

Background: A durable therapeutic relationship is central to mental health practice. The Working Alliance Inventory (WAI) and the Helping Alliance Questionnaire (HAQ) are established instruments for measuring such a relationship. Aims: The project aimed to test the correlation between the two scales for patients with severe psychotic illness treated in an Assertive Community Treatment (ACT) team. Methods: Ninety-one patients of an ACT team and their key-workers were recruited to complete the measures. Results: Seventy-one patients (78%) completed the scales, and key-workers completed scales for every eligible patient. Both groups rated the relationship positively. There was a strong and significant correlation between the patient version of the WAI and the HAQ. There were significant but much weaker correlations between the patient-rated WAI and HAQ and the key-worker WAI. Conclusion: The patient version of the WAI and the HAQ seem to measure the patient's view of the relationship equivalently. The HAQ is simpler and easier to administer than the WAI.