bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Bactericidal Activities of High-Dose Daptomycin with and without Coadministration of Gentamicin against Isolates of
Staphylococcus aureus
and
Enterococcus
species
Authors: DeRyke C. Andrew , Sutherland Christina , Zhang Bo , Nicolau David P. , Kuti Joseph L. 
Published: October 2006

ABSTRACT

The purpose of this experiment was to evaluate the pharmacokinetics and serum bactericidal titers (SBTs) of daptomycin alone and in combination with gentamicin against strains of
Staphylococcus aureus
and enterococci to determine if there might be any benefit to the addition of the aminoglycoside. A multiple-dose, randomized crossover study was performed in 11 healthy volunteers to evaluate the steady-state pharmacokinetic profile of 6 mg/kg of body weight daptomycin once daily with or without 1 mg/kg gentamicin every 8 h. SBTs were determined against clinical isolates of nosocomial (MRSA 494) and community-acquired (CA-MRSA 44) methicillin-resistant
S. aureus
, vancomycin-susceptible
Enterococcus faecalis
(VSEF 49452), vancomycin-resistant
Enterococcus faecium
(VREF 80), and quality control strains of methicillin-susceptible
S. aureus
(ATCC 29213) and vancomycin-susceptible
E. faecalis
(ATCC 29212). Enhancement of bactericidal activity was evaluated by calculating and comparing the areas under the bactericidal curve (AUBC) for each dosing regimen against each isolate. The area under the concentration-time curve from 0 to 24 h and clearance for daptomycin alone were 645 ± 91 μg · h/ml and 9.47 ± 1.4 mg/h/kg, respectively, compared with 642 ± 69 μg · h/ml and 9.45 ± 1.0 mg/h/kg for daptomycin plus gentamicin. Daptomycin alone displayed sustained bactericidal activity against five of the six isolates over the entire 24-h dosing interval; bactericidal activity was maintained for 8 h against VREF 80. Mean AUBCs for daptomycin alone ranged from 935 to 1,263 and 36 to 238 against staphylococcal and enterococcal isolates, respectively, compared with 902 to 972 and 34 to 213 against staphylococci and enterococci when coadministered with gentamicin. The results of this study suggest that the addition of gentamicin does not alter the pharmacokinetic profile or enhance the bactericidal activity of daptomycin against staphylococcal or enterococcal isolates.
Population Pharmacokinetics of Arbekacin in Patients Infected with Methicillin-Resistant
Staphylococcus aureus
Authors: Tanigawara Yusuke , Sato Reiko , Morita Kunihiko , Kaku Mitsuo , Aikawa Naoki , Shimizu Kihachiro 
Published: October 2006

ABSTRACT

Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant
Staphylococcus aureus
(MRSA). The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers. The age of the study population ranged from 8 to 95 years, and weight ranged from 10.8 to 107 kg. In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis. Drug concentration-time data were well described by a two-compartment open model. Factors influencing arbekacin pharmacokinetics were investigated using a nonlinear mixed-effect model analysis. The best-developed model showed that drug clearance (CL) was related to creatinine clearance (CL
CR
), age, and body weight (WT), as expressed by CL (liter/h) = 0.0319CL
CR
+ (26.5/age) (CL
CR
< 80 ml/min) and CL (liter/h) = 0.0130 CL
CR
+ 0.0342WT + (26.5/age) (CL
CR
≥ 80 ml/min). The volume of distribution for the central and peripheral compartments was different in healthy subjects and infected patients, and this difference was more pronounced among disease types. The elderly subjects (aged 80 years or over) exhibited, on average, a 19% greater volume for the central compartment. The volumes for the peripheral compartment were 50.6 liters in patients with pneumonia and 24.3 liters in patients with sepsis. The population pharmacokinetic parameters of arbekacin obtained here are useful for optimal use of this aminoglycoside in the treatment of MRSA-infected patients.
Complete Nucleotide Sequence of pK245, a 98-Kilobase Plasmid Conferring Quinolone Resistance and Extended-Spectrum-β-Lactamase Activity in a Clinical
Klebsiella pneumoniae
Isolate
Authors: Chen Ying-Tsong , Shu Hung-Yu , Li Ling-Hui , Liao Tsai-Lien , Wu Keh-Ming , Shiau Yih-Ru , Yan Jing-Jou , Su Ih-Jen , Tsai Shih-Feng , Lauderdale Tsai-Ling 
Published: October 2006

ABSTRACT

A plasmid containing the
qnrS
quinolone resistance determinant and the gene encoding the SHV-2 β-lactamase has been discovered from a clinical
Klebsiella pneumoniae
strain isolated in Taiwan. The complete 98-kb sequence of this plasmid, designated pK245, was determined by using a whole-genome shotgun approach. Transfer of pK245 conferred low-level resistance to fluoroquinolones in electroporant
Escherichia coli
epi300. The sequence of the immediate region surrounding
qnrS
in pK245 is nearly identical (>99% identity) to those of pAH0376 from
Shigella flexneri
and pINF5 from
Salmonella enterica
serovar Infantis, the two other
qnr
S-carrying plasmids reported to date, indicating a potential common origin. Other genes conferring resistance to aminoglycosides (
aacC2
,
strA
, and
strB
), chloramphenicol (
catA2
), sulfonamides (
sul
2), tetracycline (
tetD
), and trimethoprim (
dfrA14
) were also detected in pK245. The
dfrA14
gene is carried on a class I integron. Several features of this plasmid, including three separate regions containing putative replicons, a partitioning-control system, and a type II restriction modification system, suggest that it may be able to replicate and adapt in a variety of hosts. Although no critical conjugative genes were detected, multiple insertion sequence elements were found scattered throughout pK245, and these may facilitate the dissemination of the antimicrobial resistance determinants. We conclude that pK245 is a chimera which acquired its multiple antimicrobial resistance determinants horizontally from different sources. The identification of pK245 plasmid expands the repertoire of the coexistence of quinolone and extended-spectrum-β-lactam resistance determinants in plasmids carried by various species of the family
Enterobacteriaceae
in different countries.
Anidulafungin Pharmacokinetics and Microbial Response in Neutropenic Mice with Disseminated Candidiasis
Authors: Gumbo Tawanda , Drusano George L. , Liu Weiguo , Ma Lei , Deziel Mark R. , Drusano Michael F. , Louie Arnold 
Published: October 2006

ABSTRACT

Candidemia is often fatal, especially in patients with persistent neutropenia. New therapies are needed. We performed 24-h pharmacodynamic studies to compare the efficacies of anidulafungin, fluconazole, and amphotericin B in neutropenic mice with disseminated candidiasis caused by one of three strains of
Candida glabrata
. Anidulafungin produced a maximal fungal kill (
E
max
) of 1.4 to 1.9 log
10
CFU/g in kidneys and was not influenced by resistance to either fluconazole or amphotericin B. Fluconazole produced an
E
max
of 1.3 log
10
CFU/g in mice infected with fluconazole-susceptible
C. glabrata
, but the
E
max
was 0 for mice infected with a
C. glabrata
strain that had a fluconazole MIC of ≥32 mg/liter. Amphotericin B achieved an
E
max
of 4.2 log
10
CFU/g in mice infected with amphotericin B-susceptible
C. glabrata
, but the
E
max
was 0 for mice infected with a
C. glabrata
strain with an amphotericin B MIC of 2 mg/liter. In all instances, anidulafungin's maximal microbial kill was superior to that of fluconazole. Next, we performed a 96-h anidulafungin pharmacokinetic-pharmacodynamic study. Anidulafungin exhibited delayed peak concentrations in kidneys compared to those in serum, after which the concentrations declined, with a serum terminal half-life of 21.6 (±4.6) h. This was accompanied by a persistent 96-h decrease in the kidney fungal burden after treatment with a single anidulafungin dose of ≥8 mg/kg of body weight. This pharmacokinetic-pharmacodynamic picture of anidulafungin persistence in tissues and the resultant persistent fungal decline should be exploited to improve the efficacy of anidulafungin therapy for candidemia.
The Anti-Methicillin-Resistant
Staphylococcus aureus
Quinolone WCK 771 Has Potent Activity against Sequentially Selected Mutants, Has a Narrow Mutant Selection Window against Quinolone-Resistant
Staphylococcus aureus
, and Preferentially Targets DNA Gyrase
Authors: Bhagwat Sachin S. , Mundkur Lakshmi A. , Gupte Shrikant V. , Patel Mahesh V. , Khorakiwala Habil F. 
Published: October 2006

ABSTRACT

WCK 771 is a broad-spectrum fluoroquinolone with enhanced activity against quinolone-resistant staphylococci. To understand the impact of the target-level interactions of WCK 771 on its antistaphylococcal pharmacodynamic properties, we determined the MICs for genetically defined mutants and studied the mutant prevention concentrations (MPCs), the frequency of mutation, and the cidality against the wild type and double mutants. There was a twofold increase in the MICs of WCK 771 for single
gyrA
mutants, indicating that DNA gyrase is its primary target. All first- and second-step mutants selected by WCK 771 revealed
gyrA
and
grlA
mutations, respectively. The MICs of WCK 771 and clinafloxacin were found to be superior to those of other quinolones against strains with double and triple mutations. WCK 771 was also cidal for high-density double mutants at low concentrations. WCK 771 and clinafloxacin showed narrow mutant selection windows compared to those of the other quinolones. Against a panel of 50 high-level quinolone-resistant clinical isolates of staphylococci (ciprofloxacin MIC ≥ 16 μg/ml), the WCK 771 MPCs were ≤2 μg/ml for 68% of the strains and ≤4 μg/ml for 28% of the strains. Our results demonstrate that
gyrA
is the primary target of WCK 771 and that it has pharmacodynamic properties remarkably different from those of quinolones with dual targets (garenoxacin and moxifloxacin) and topoisomerase IV-specific quinolones (trovafloxacin). WCK 771 displayed an activity profile comparable to that of clinafloxacin, a dual-acting quinolone with a high affinity to DNA gyrase. Overall, the findings signify the key role of DNA gyrase in determining the optimal antistaphylococcal features of quinolones.
Molecular Basis for Enhanced Activity of Posaconazole against
Absidia corymbifera
and
Rhizopus oryzae
Authors: Chau Andrew S. , Chen Guodong , McNicholas Paul M. , Mann Paul A. 
Published: October 2006

ABSTRACT

Posaconazole and itraconazole were more potent inhibitors of ergosterol synthesis, in both intact cells and cell extracts from
Absidia corymbifera
and
Rhizopus oryzae
, than voriconazole and fluconazole. Similarly, expression of CYP51 from
R. oryzae
in
Saccharomyces cerevisiae
significantly increased resistance to fluconazole and voriconazole but not to posaconazole and itraconazole.
Combinations of R207910 with Drugs Used To Treat Multidrug-Resistant Tuberculosis Have the Potential To Shorten Treatment Duration
Authors: Lounis Nacer , Veziris Nicolas , Chauffour Aurélie , Truffot-Pernot Chantal , Andries Koen , Jarlier Vincent 
Published: October 2006

ABSTRACT

The objective of the present study was to identify the optimal R207910-containing regimen to administer to patients who cannot receive rifampin (RIF) and isoniazid (INH) because of multidrug-resistant tuberculosis (MDR-TB), concomitant use of antiretroviral drugs, or toxicity. Mice were infected intravenously with 5 × 10
6
CFU of the H37Rv strain and treated five times per week with R207910 alone or various combinations of R207910 with the second-line drugs amikacin (AMK), pyrazinamide (PZA), moxifloxacin (MXF), and ethionamide (ETH). All R207910-containing regimens were significantly more active than the non-R207910-containing regimens after 1 month of therapy. When given for 2 months, R207910 alone was more active than the WHO standard first-line regimen RIF-INH-PZA. When R207910 was combined with second-line drugs, the combinations were more active than the currently recommended regimen of MDR-TB AMK-ETH-MXF-PZA, and culture negativity of both the lungs and spleen was reached after 2 months of treatment in almost every case.
Interaction between Miltefosine and Amphotericin B: Consequences for Their Activities towards Intestinal Epithelial Cells and
Leishmania donovani
Promastigotes In Vitro
Authors: Ménez Cécile , Buyse Marion , Besnard Madeleine , Farinotti Robert , Loiseau Philippe M. , Barratt Gillian 
Published: October 2006

ABSTRACT

The aim of this study was to evaluate the potential of a combination of two antileishmanial drugs, miltefosine (HePC) and amphotericin B (AMB), when administered by the oral route. Caco-2 cell monolayers were used as a validated in vitro model of the intestinal barrier and
Leishmania donovani
promastigotes as a model for evaluating the effect of the drug combination. Spectroscopic measurements demonstrated that HePC and AMB associate, leading to the formation of mixed aggregates in which AMB is solubilized as monomers. The incubation of the association of HePC and AMB with Caco-2 cell monolayers, at a concentration higher than 5 μM, led to (i) a reduction of the HePC-induced paracellular permeability enhancement in Caco-2 cell monolayers, (ii) an inhibition of the uptake of both drugs, and (iii) a decrease in the transepithelial transport of both drugs, suggesting that a pharmacokinetic antagonism between HePC and AMB could occur after their oral administration. However, the combination did not exhibit any antagonism or synergy in its antileishmanial activity. These results demonstrated a strong physicochemical interaction between HePC and AMB, depending on the concentration of each, which could have important consequences for their biological activities, if they are administered together.
Efficacy of Novel Rifamycin Derivatives against Rifamycin-Sensitive and -Resistant
Staphylococcus aureus
Isolates in Murine Models of Infection
Authors: Rothstein David M. , Farquhar Ronald S. , Sirokman Klari , Sondergaard Karen L. , Hazlett Charles , Doye Angelia A. , Gwathmey Judith K. , Mullin Steve , van Duzer John , Murphy Christopher K. 
Published: October 2006

ABSTRACT

Novel rifamycins (new chemical entities [NCEs]) having MICs of 0.002 to 0.03 μg/ml against
Staphylococcus aureus
and retaining some activity against rifampin-resistant mutants were tested for in vivo efficacy against susceptible and rifampin-resistant strains of
S. aureus
. Rifalazil and rifampin had a 50% effective dose (ED
50
) of 0.06 mg/kg of body weight when administered as a single intravenous (i.v.) dose in a murine septicemia model against a susceptible strain of
S. aureus.
The majority of NCEs showed efficacy at a lower i.v. dose (0.003 to 0.06 mg/kg). In addition, half of the NCEs tested for oral efficacy had ED
50
s in the range of 0.015 to 0.13 mg/kg, i.e., lower or equivalent to the oral ED
50
s of rifampin and rifalazil. NCEs were also tested in the septicemia model against a rifampin-resistant strain of
S. aureus
. Twenty-four of 169 NCEs were efficacious when administered as a single oral dose of 80 mg/kg. These NCEs were examined in the murine thigh infection model against a susceptible strain of
S. aureus
. Several NCEs dosed by intraperitoneal injection at 0.06 mg/kg caused a significant difference in bacterial titer compared with placebo-treated animals. No NCEs showed efficacy in the thigh model against a highly rifampin-resistant strain. However, several NCEs showed an effect when tested against a partially rifampin-resistant strain. The NCEs having a 25-hydroxyl moiety were more effective as a group than their 25-
O
-acetyl counterparts. These model systems defined candidate NCEs as components of potential combination therapies to treat systemic infections or as monotherapeutic agents for topical applications.
The effect of breathing an ambient low-density, hyperoxic gas on the perceived effort of breathing and maximal performance of exercise in well-trained athletes
Authors: Ansley L , Petersen D , Thomas A , St Clair Gibson A , Robson-Ansley P , Noakes T D 
Published: October 2006

Background:The role of the perception of breathing effort in the regulation of performance of maximal exercise remains unclear.Aims:To determine whether the perceived effort of ventilation is altered through substituting a less dense gas for normal ambient air and whether this substitution affects performance of maximal incremental exercise in trained athletes.Methods:Eight highly trained cyclists (mean SD) maximal oxygen consumption (VO2max) = 69.9 (7.9) (mlO2/kg/min) performed two randomised maximal tests in a hyperbaric chamber breathing ambient air composed of either 35% O2/65% N2(nitrox) or 35% O2/65% He (heliox). A ramp protocol was used in which power output was incremented at 0.5 W/s. The trials were separated by at least 48 h. The perceived effort of breathing was obtained via Borg Category Ratio Scales at 3-min intervals and at fatigue. Oxygen consumption (VO2) and minute ventilation (VE) were monitored continuously.Results:Breathing heliox did not change the sensation of dyspnoea: there were no differences between trials for the Borg scales at any time point. Exercise performance was not different between the nitrox and heliox trials (peak power output = 451 (58) and 453 (56) W), nor was VO2max (4.96 (0.61) and 4.88 (0.65) l/min) or maximal VE(157 (24) and 163 (22) l/min). Between-trial variability in peak power output was less than either VO2max or maximal VE.Conclusion:Breathing a less dense gas does not improve maximal performance of exercise or reduce the perception of breathing effort in highly trained athletes, although an attenuated submaximal tidal volume and VEwith a concomitant reduction in VO2suggests an improved gas exchange and reduced O2cost of ventilation when breathing heliox.
Comparison of once-weekly and twice-weekly strength training in older adults
Authors: DiFrancisco-Donoghue J , Werner W , Douris P C 
Published: October 2006

Background:Strength training has been shown to benefit the health and function of older adults.Objective:To investigate whether one set of exercises performed once a week was as effective in increasing muscle strength as training twice a week.Methods:18 subjects (7 women and 11 men) aged 65–79 years were randomly assigned to two groups. Both groups performed one set of exercises to muscular fatigue; group 1 trained 1 day/week and group 2 trained 2 days/week on three lower and three upper body exercises for 9 weeks. The data were analysed using a mixed model 2×2 analysis of variance.Results:A significant main effect of time (p<0.001), but not group, on one-repetition maximum scores was observed. No significant interaction was observed between time and group and therefore no difference in strength changes between training once a week versus twice a week after 9 weeks.Conclusions:One set of exercises performed once weekly to muscle fatigue improved strength as well as twice a week in the older adult. Our results provide information that will assist in designing strength-training programmes that are more time and cost efficient in producing health and fitness benefits for older adults.
Chronic tendinopathy: effectiveness of eccentric exercise
Authors: Woodley Brett L , Newsham-West Richard J , Baxter G David 
Published: October 2006

Objectives:To determine the effectiveness of eccentric exercise (EE) programmes in the treatment of common tendinopathies.Data sources:Relevant randomised controlled trials (RCTs) were sourced using the OVID website databases: MEDLINE (1966–Jan 2006), CINAHL (1982–Jan 2006), AMED (1985–Jan 2006), EMBASE (1988–Jan 2006), and all EBM reviews – Cochrane DSR, ACP Journal Club, DARE, and CCTR (Jan 2006). The Physiotherapy Evidence Database (PEDro) was also searched using the keyword: eccentric.Review methods:The PEDro and van Tulder scales were employed to assess methodological quality. Levels of evidence were then obtained according to predefined thresholds:Strong–consistent findings among multiple high-quality RCTs.Moderate–consistent findings among multiple low-quality RCTs and/or clinically controlled trials (CCTs) and/or one high-quality RCT.Limited–one low-quality RCT and/or CCT.Conflicting–inconsistent findings among multiple trials (RCTs and/or CCTs).No evidence–no RCTs or CCTs.Results:Twenty relevant studies were sourced, 11 of which met the inclusion criteria. These included studies of Achilles tendinopathy (AT), patella tendinopathy (PT) and tendinopathy of the common wrist extensor tendon of the lateral elbow (LET). Limited levels of evidence exist to suggest that EE has a positive effect on clinical outcomes such as pain, function and patient satisfaction/return to work when compared to various control interventions such as concentric exercise (CE), stretching, splinting, frictions and ultrasound. Levels of evidence were found to be variable across the tendinopathies investigated.Conclusions:This review demonstrates the dearth of high-quality research in support of the clinical effectiveness of EE over other treatments in the management of tendinopathies. Further adequately powered studies that include appropriate randomisation procedures, standardised outcome measures and long-term follow-up are required.
The Absolute Risk of Cervical Abnormalities in High-risk Human Papillomavirus–Positive, Cytologically Normal Women Over a 10-Year Period
Authors: Kjaer Susanne , Høgdall Estrid , Frederiksen Kirsten , Munk Christian , van den Brule Adriaan , Svare Edith , Meijer Chris , Lorincz Attilla , Iftner Thomas 
Published: October 2006

Abstract
In spite of the success of cervical cytology as a cancer-screening tool, it has important limitations, and human papillomavirus (HPV) testing may be valuable in future screening. The majority of women in screened populations, who test HPV positive, will have a concurrent normal smear, and we need more information about the risk for subsequent high-grade cervical lesions in these women. We examined 8,656 younger women (22–32 years old) and 1,578 older women (40–50 years old) who were followed for development of cervical neoplasia (cytology and/or histology) through the Danish Pathology Data Bank. We estimated the proportion of women developing cervical lesions of different types before a given time point as a function of time. Among women with normal cytology and positive high-risk Hybrid Capture 2 (HC2) test, 17.7% and 24.5% of younger and older women, respectively, had a subsequent abnormal Pap smear within 5 years. The risk of CIN3 or cancer within 10 years among younger women with positive HC2 test was 13.6% (10.9–16.2) and 21.2% (2.7–36.1) among older women. An analysis among younger women also being HC2-positive 2 years before baseline showed a subsequent 10-year risk of ≥CIN3 of 18% (14.6–21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of ≥CIN3 in HC2-positive women was more than 20% within 10 years. These results indicate that even a single positive HPV test in cytologically negative women is substantially predictive of high-grade CIN and suggest that HC2 testing can help stratify women into different risk categories. (Cancer Res 2006; 66(21): 10630-6)