bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Activities of Daptomycin, Arbekacin, Vancomycin, and Gentamicin Alone and/or in Combination against Glycopeptide Intermediate-Resistant
Staphylococcus aureus
in an Infection Model
Authors: Akins Ronda L. , Rybak Michael J. 
Published: July 2002

ABSTRACT

Daptomycin, a lipopeptide antibiotic, has broad activity against gram-positive organisms, similar to vancomycin; however, its mechanism of action differs, resulting in interference with cell membrane transport and a more rapid bactericidal activity. In light of increasing need for alternative treatments against intermediate-resistant
Staphylococcus aureus
, there is revitalized interest in this antibiotic. We, therefore, evaluated the activity of daptomycin alone or in combination in an in vitro infection model against two glycopeptide intermediate-resistant
S. aureus
(GISA) isolates. Newly designed regimens of daptomycin at 4 and 6 mg/kg of body weight every 24 h (q24h) were compared to the previous regimen of 3 mg/kg q12h. Daptomycin MICs and minimal bactericidal concentrations (MBCs) (MIC/MBC) for Mu-50, HIP5836 (992), and MRSA-67 were 0.5/1.0, 0.5/1.0, and 0.125/0.5 μg/ml, respectively. MICs and MBCs of arbekacin for the three strains were 2.0/8.0, 0.125/0.5, and 0.125/0.25 μg/ml, respectively. Vancomycin and gentamicin MICs and MBCs for the three strains were 8.0/8.0, 8.0/8.0, and 0.5/1.0 μg/ml and 128/128, 0.5/1.0, and 0.25/0.5 μg/ml, respectively. Our experience with daptomycin in an in vitro infection model has shown significant kill against the two GISA strains (Mu-50 and 992) (
P
< 0.03). We also noted that kill was related to a total dose effect for 992, in which simulated daptomycin in vivo dosages of 6 mg/kg q24h and 3 mg/kg q12h produced similar kill and 4 mg/kg q24h resulted in significant regrowth (
P
≤ 0.05). Combination therapy with arbekacin resulted in synergistic activity against Mu-50. Daptomycin area under the concentration-time curve/MIC and
C
max
/MIC ranges for GISA isolates were 80 to 116 and 6 to 12, respectively, and ranges for MRSA-67 were 320 to 461 and 24 to 48, respectively, and appeared to have an association with kill (i.e., decreased CFU/milliliter) at 24 and 48 h. Therefore, these experiments suggest that daptomycin alone or in combination could provide an alternative for the treatment of GISA.
Susceptibility Testing of
Malassezia
Species Using the Urea Broth Microdilution Method
Authors: Nakamura Yuka , Kano Rui , Murai Tae , Watanabe Shinichi , Hasegawa Atsuhiko 
Published: July 2002

ABSTRACT

A urea broth microdilution method to assay the susceptibilities of seven
Malassezia
species was developed. This method indicated the same sensitivities as the agar plate dilution method for isolates of
Malassezia furfur
,
M. pachydermatis
,
M. slooffiae
, and
M. sympodialis
.
Analysis of Ciprofloxacin Activity against
Streptococcus pneumoniae
after 10 Years of Use in the United States
Authors: Sahm Daniel F. , Peterson Dan E. , Critchley Ian A. , Thornsberry Clyde 
Published: July 2002

ABSTRACT

As the most commonly used fluoroquinolone in the United States since 1987, ciprofloxacin has exerted the greatest selective pressure on
S. pneumoniae
and provides a valuable marker to evaluate the actual and potential emergence of fluoroquinolone resistance in this species. Analysis of susceptibility results obtained with 5,640 strains collected from throughout the United States showed that only 16 (0.3%) of the isolates demonstrated MICs of ≥4 μg/ml. The prevalence of this phenotype was significantly higher (
P
< 0.05) among penicillin-resistant populations, among isolates from patients >64 years old, and among respiratory isolates. However, >99% of strains had MICs of <4 μg/ml regardless of the risk group examined, and the MIC population distributions were the same for each risk group. These findings demonstrate that the phenotype of a MIC of ≥4 μg/ml remains uncommon after 10 years of ciprofloxacin use; however, these findings are no reason to become complacent with regard to appropriate use of fluoroquinolones and the need to carefully track resistance trends. Equally important is careful analysis of data that result from surveillance in terms of risk factors and other associated trends so that resistance and susceptibility, and their consequences, are neither over- nor underestimated.
Inducible Azole Resistance Associated with a Heterogeneous Phenotype in
Candida albicans
Authors: Marr Kieren A. , Lyons Christopher N. , Ha Kien , Rustad Tige R. , White Theodore C. 
Published: July 2002

ABSTRACT

The development of azole resistance in
Candida albicans
is most problematic in patients with AIDS who receive long courses of drug for therapy or prevention of oral candidiasis. Recently, the rapid development of resistance was noted in other immunosuppressed patients who developed disseminated candidiasis despite fluconazole prophylaxis. One of these series of
C. albicans
isolates became resistant, with an associated increase in mRNA specific for a
CDR
ATP-binding cassette transporter efflux pump (K. A. Marr, C. N. Lyons, T. R. Rustad, R. A. Bowden, and T. C. White, Antimicrob. Agents Chemother. 42:2584–2589, 1998). Here we study this series of
C. albicans
isolates further and examine the mechanism of azole resistance in a second series of
C. albicans
isolates that caused disseminated infection in a recipient of bone marrow transplantation. The susceptible isolates in both series become resistant to fluconazole after serial growth in the presence of drug, while the resistant isolates in both series become susceptible after serial transfer in the absence of drug. Population analysis of the inducible, transiently resistant isolates reveals a heterogeneous population of fluconazole-susceptible and -resistant cells. We conclude that the rapid development of azole resistance occurs by a mechanism that involves selection of a resistant clone from a heterogeneous population of cells.
High Therapeutic Index of Factor C Sushi Peptides: Potent Antimicrobials against
Pseudomonas aeruginosa
Authors: Yau Yin Hoe , Ho Bow , Tan Nguan Soon , Ng Miang Lon , Ding Jeak Ling 
Published: July 2002

ABSTRACT

Factor C protein isolated from the horseshoe crab,
Carcinoscorpius rotundicauda
, has endotoxin binding capability. Synthetic peptides of 34 amino acids based on the sequence of two regions of factor C (Sushi 1 and Sushi 3) as well as their corresponding mutants exhibited activities against 30 clinical isolates of
Pseudomonas aeruginosa
. Collectively, all four peptides demonstrated exceptionally effective bactericidal activity against
P. aeruginosa
with 90% minimal bactericidal concentrations (MBC
90
s) in the range of 0.06 to 0.25 μg/ml (16 to 63 nM). Viable bacteria were reduced by 90% after 7 min and were totally eradicated within 40 to 50 min. These peptides are minimally hemolytic against both rabbit and human erythrocytes even at concentrations up to 1,600-fold their MBC
90
s. Both in vitro and in vivo studies indicate that cytotoxic effects are small even at 1,000-fold their MBC
90
s. Furthermore, the Sushi peptides are tolerant of high-salt and adverse pH conditions. These findings demonstrate the promising therapeutic potential of the Sushi peptides.
Compartmental Pharmacokinetics and Tissue Distribution of the Antifungal Echinocandin Lipopeptide Micafungin (FK463) in Rabbits
Authors: Groll Andreas H. , Mickiene Diana , Petraitis Vidmantas , Petraitiene Ruta , Ibrahim Khalid H. , Piscitelli Stephen C. , Bekersky Ihor , Walsh Thomas J. 
Published: July 2002

ABSTRACT
The plasma pharmacokinetics and tissue distribution of the novel antifungal echinocandin-like lipopeptide micafungin (FK463) were investigated in healthy rabbits. Cohorts of three animals each received micafungin at 0.5, 1, and 2 mg/kg of body weight intravenously once daily for a total of 8 days. Serial plasma samples were collected on days 1 and 7, and tissue samples were obtained 30 min after the eighth dose. Drug concentrations were determined by validated high-performance liquid chromatographic methods. Plasma drug concentration data were fit to a two-compartment pharmacokinetic model, and pharmacokinetic parameters were estimated using weighted nonlinear least-square regression analysis. Micafungin demonstrated linear plasma pharmacokinetics without changes in total clearance and dose-normalized area under the concentration-time curve from 0 h to infinity. After administration of single doses to the rabbits, mean peak plasma drug concentrations ranged from 7.62 μg/ml at 0.5 mg/kg to 16.8 μg/ml at 2 mg/kg, the area under the concentration-time curve from 0 to 24 h ranged from 5.66 to 21.79 μg · h/ml, the apparent volume of distribution at steady state ranged from 0.296 to 0.343 liter/kg, and the elimination half-life ranged from 2.97 to 3.20 h, respectively. No significant changes in pharmacokinetic parameters and no accumulation was noted after multiple dosing. Mean tissue micafungin concentrations 30 min after the last of eight daily doses were highest in the lung (2.26 to 11.76 μg/g), liver (2.05 to 8.82 μg/g), spleen (1.87 to 9.05 μg/g), and kidney (1.40 to 6.12 μg/g). While micafungin was not detectable in cerebrospinal fluid, the concentration in brain tissue ranged from 0.08 to 0.18 μg/g. These findings indicate linear disposition of micafungin at dosages of 0.5 to 2 mg/kg and achievement of potentially therapeutic drug concentrations in plasma and tissues that are common sites of invasive fungal infections.
Rapid and Simple Phenotypic Assay for Drug Susceptibility of Human Immunodeficiency Virus Type 1 Using CCR5-Expressing HeLa/CD4
+
Cell Clone 1-10 (MAGIC-5)
Authors: Hachiya Atsuko , Aizawa-Matsuoka Saori , Tanaka Mari , Takahashi Yukiko , Ida Setsuko , Gatanaga Hiroyuki , Hirabayashi Yoshihiro , Kojima Asato , Tatsumi Masashi , Oka Shinichi 
Published: July 2002

ABSTRACT

We describe a rapid and simple novel phenotypic assay for drug susceptibility of human immunodeficiency virus type-1 (HIV-1) using a CCR5-expressing HeLa/CD4
+
cell clone 1-10 (MAGIC-5). MAGIC-5 cells produced large amounts of HIV-1 in culture supernatants, which enabled us to perform the phenotypic resistance assay. Determination of HIV-1 susceptibility to various protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors was completed within 15 days in T-cell-tropic (X4) and macrophage-tropic (R5) viruses using fresh plasma samples containing at least 10
4
copies/ml. The nucleotide sequence of the envelope V3 region of HIV-1 in plasma was almost identical to that of the virus isolated by MAGIC-5 cells, suggesting a lack of selection bias in our assay. The assay variability was confined to within five-fold in all drugs examined. Accordingly, we used a 10-fold increase in the 50% inhibitory concentration as the cutoff value for viral resistance in the present assay. HIV-1 resistant to lamivudine, which was not detected by conventional genotypic assays, was isolated. In HIV-1 with PI-associated primary amino acid substitutions, our assay showed that drug resistance profiles correlated well with previously reported genotypic-assay data. Furthermore, our assay provided comprehensive results regarding PI resistance in the presence of multiple mutations. The novel assay successfully quantified the level of resistance of clinical HIV-1 isolates to a battery of anti-HIV drugs, indicating its clinical usefulness, particularly in patients who failed to respond to antiretroviral chemotherapy.
Characterization of OXA-25, OXA-26, and OXA-27, Molecular Class D β-Lactamases Associated with Carbapenem Resistance in Clinical Isolates of
Acinetobacter baumannii
Authors: Afzal-Shah Mariya , Woodford Neil , Livermore David M. 
Published: July 2002

ABSTRACT

Carbapenem resistance in
Acinetobacter
spp. is increasingly being associated with OXA-type β-lactamases with weak hydrolytic activity against imipenem and meropenem. Such enzymes were characterized from
Acinetobacter
isolates collected in Belgium, Kuwait, Singapore, and Spain. The isolates from Spain and Belgium had novel class D β-lactamases that were active against carbapenems. These were designated OXA-25 and OXA-26, respectively, and had >98% amino acid homology with each other and with the OXA-24 enzyme recently described by others from an
Acinetobacter
isolate collected elsewhere in Spain. The isolate from Singapore had OXA-27 β-lactamase, another novel class D type with only 60% homology to OXA-24, -25, and -26, but with 99% homology to OXA-23 (ARI-1), described previously from an
Acinetobacter baumannii
isolate collected in Scotland. Sequence data were not obtained for the carbapenem-hydrolyzing OXA enzyme from the isolate from Kuwait; nevertheless, the enzyme was phenotypically similar to OXA-25 and -26. The enzymes OXA-23, -24, -25, -26, and -27 retained the STFK and SXV motifs typical of class D β-lactamases, but the YGN motif was altered to FGN. The KTG motif was retained by OXA-27 and -23 but was replaced by KSG in OXA-24, -25, and -26. OXA-25 and -26 enzymes were strongly active against oxacillin, but unusually for an OXA-type β-lactamase, OXA-27 had apparently weak activity, although measurement was complicated by biphasic kinetics. None of the new enzymes was transmissible to
Escherichia coli
recipients. Many
Acinetobacter
isolates are multiresistant to other antibiotics, and the emergence of class D enzymes with carbapenem-hydrolyzing activity is a disturbing development for antimicrobial chemotherapy.
Comparative Toxicities and Pharmacokinetics of Intrathecal Lipid (Amphotericin B Colloidal Dispersion) and Conventional Deoxycholate Formulations of Amphotericin B in Rabbits
Authors: Clemons Karl V. , Sobel Raymond A. , Williams Paul L. , Stevens David A. 
Published: July 2002

ABSTRACT
The lipid formulation of amphotericin B, Amphotec (ABCD), has not been used intrathecally. After a single intrathecal dose or after four doses, conventionally formulated deoxycholate amphotericin B (AMB) (Fungizone) resulted in higher levels of amphotericin B in the cerebrospinal fluid of rabbits than did ABCD. Clinically and histologically, ABCD was about threefold less toxic than AMB after a single dose and 3- to 30-fold less toxic after multiple dosing. These data are encouraging for the potential use of ABCD as an intrathecal treatment.
Identification of β-Lactamase-Negative, Ampicillin-Resistant Strains of
Haemophilus influenzae
with Four Methods and Eight Media
Authors: Barry Arthur L. , Fuchs Peter C. , Brown Steven D. 
Published: July 2002

ABSTRACT

A challenge set of 143 non-β-lactamase-producing strains of
Haemophilus influenzae
was tested for ampicillin susceptibility on two broth media and six agar media, using broth microdilution, agar dilution, disk diffusion, and E-test procedures. When β-lactamase-negative, ampicillin-resistant (BLNAR) strains were defined as those for which the ampicillin MIC was ≥4.0 μg/ml, 5 to 44% of our selected strains were BLNAR depending on the medium and/or test method used. If nonsusceptible strains for which ampicillin MICs were intermediate were included in the BLNAR category, 32 to 50% of our isolates would be considered BLNAR. These data emphasize the need for a standardized testing procedure and a universal definition of BLNAR strains before the clinical relevance of such strains can be evaluated. NCCLS dilution tests with haemophilus test medium broth or agar are preferred for testing ampicillin against
H. influenzae
.
Occurrence and Risk of Cochleotoxicity in Cystic Fibrosis Patients Receiving Repeated High-Dose Aminoglycoside Therapy
Authors: Mulheran M. , Degg C. , Burr S. , Morgan D. W. , Stableforth D. E. 
Published: July 2002

ABSTRACT
Cystic fibrosis (CF) patients receive repeated courses of aminoglycoside therapy. These patients would consequently be expected to be more susceptible to cochleotoxicity, a recognized side effect with single courses of aminoglycoside therapy. The primary aim of this retrospective study was to establish the incidence and severity of auditory deficit in CF patients. Standard (0.25- to 8-kHz) and high-frequency (10- to 16-kHz) pure-tone audiometry was carried out in 70 CF patients, and the results were compared with the results from 91 control subjects. These subjects were further divided into pediatric and adult groups. Of 70 CF patients, 12 (1 pediatric) displayed hearing loss considered to be caused by repeated exposure to aminoglycosides. There was a nonlinear relationship between the courses of therapy received and the incidence of hearing loss. The severity of the loss did not appear to be related to the number of courses received. Assuming the risk of loss to be independent for each course, preliminary estimates of per course risk of hearing loss were less than 2%. Upon comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than would be expected, suggesting that the CF condition may confer protection against aminoglycoside cochleotoxicity.
CTX-M-1, CTX-M-3, and CTX-M-14 β-Lactamases from
Enterobacteriaceae
Isolated in France
Authors: Dutour C. , Bonnet R. , Marchandin H. , Boyer M. , Chanal C. , Sirot D. , Sirot J. 
Published: July 2002

ABSTRACT

Six clinical CTX-M-producing isolates of the family
Enterobacteriaceae
were detected between 1999 and 2000 in different French hospitals. Two strains produced CTX-M-1 and CTX-M-3 and four strains produced CTX-M-14, a mutant Ala-231→Val of CTX-M-9. A putative transposable element, ISEcp-1, was located 43 bp upstream of all the
bla
CTX-M
genes. Two CTX-M-14-encoding plasmids exhibited similar restriction patterns. The CTX-M-1- and CTX-M-3-encoding plasmids were related to the CTX-M-1- and CTX-M-3-encoding plasmids previously reported in 1990 in France and in 1998 in Poland, respectively.
Rates and Extents of Antifungal Activities of Amphotericin B, Flucytosine, Fluconazole, and Voriconazole against
Candida lusitaniae
Determined by Microdilution, Etest, and Time-Kill Methods
Authors: Ernst Erika J. , Yodoi Keiko , Roling Ellen E. , Klepser Michael E. 
Published: July 2002

ABSTRACT

Amphotericin B, flucytosine, fluconazole, and voriconazole alone and in combination were evaluated against isolates of
Candida lusitaniae
. MICs were determined by broth microdilution and Etest, and time-kill studies were conducted. Amphotericin B resulted in fungicidal activity against most isolates, whereas fluconazole, voriconazole, and flucytosine produced primarily fungistatic activities. The addition of flucytosine to amphotericin B resulted in a faster rate and greater extent of kill for isolates for which the MICs of amphotericin B were elevated.
Identification of Essential Residues in the Erm(B) rRNA Methyltransferase ofClostridium perfringens
Authors: Farrow Kylie A. , Lyras Dena , Polekhina Galina , Koutsis Katerina , Parker Michael W. , Rood Julian I. 
Published: July 2002

ABSTRACTMacrolide-lincosamide-streptogramin B resistance is widespread, with the determinants encoding resistance to antibiotics such as erythromycin being detected in many bacterial pathogens. Resistance is most commonly mediated by the production of an Erm protein, a 23S rRNA methyltransferase. We have undertaken a mutational analysis of the Erm(B) protein fromClostridium perfringenswith the objective of developing a greater understanding of the mechanism of action of this protein. A recombinant plasmid that carried theerm(B) gene was mutated by either in vitro hydroxylamine mutagenesis or passage through the mutator strain XL1-Red. Twenty-eight independently derived mutants were identified, nine of which had single point mutations in theerm(B) gene. These mutants produced stable but nonfunctional Erm(B) proteins, and all had amino acid changes within conserved methyltransferase motifs that were important for either substrate binding or catalysis. Modeling of theC. perfringensErm(B) protein confirmed that the point mutations all involved residues important for the structure and/or function of this rRNA methyltransferase. These regions of the protein therefore represent potential targets for the rational development of methyltransferase inhibitors.
Intrapulmonary Pharmacokinetics of Linezolid
Authors: Conte John E. , Golden Jeffrey A. , Kipps Juliana , Zurlinden Elisabeth 
Published: July 2002

ABSTRACTIn this study, our objective was to determine the steady-state intrapulmonary concentrations and pharmacokinetic parameters of orally administered linezolid in healthy volunteers. Linezolid (600 mg every 12 h for a total of five doses) was administered orally to 25 healthy adult male subjects. Each subgroup contained five subjects, who underwent bronchoscopy and bronchoalveolar lavage (BAL) 4, 8, 12, 24, or 48 h after administration of the last dose. Blood was obtained for drug assay prior to administration of the first dose and fifth dose and at the completion of bronchoscopy and BAL. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method, and the total number of alveolar cells (AC) was counted in a hemocytometer after cytocentrifugation. Linezolid was measured in plasma by a high-pressure liquid chromatography (HPLC) technique and in BAL specimens and AC by a combined HPLC-mass spectrometry technique. Areas under the concentration-time curves (AUCs) for linezolid in plasma, ELF, and AC were derived by noncompartmental analysis. Half-lives for linezolid in plasma, ELF, and AC were calculated from the elimination rate constants derived from a monoexponential fit of the means of the observed concentrations at each time point. Concentrations (means ± standard deviations) in plasma, ELF, and AC, respectively, were 7.3 ± 4.9, 64.3 ± 33.1, and 2.2 ± 0.6 μg/ml at the 4-h BAL time point and 7.6 ± 1.7, 24.3 ± 13.3, and 1.4 ± 1.3 μg/ml at the 12-h BAL time point. Linezolid concentrations in plasma, ELF, and AC declined monoexponentially, with half-lives of 6.9, 7.0, and 5.7 h, respectively. For a MIC of 4, the 12-h plasma AUC/MIC and maximum concentration/MIC ratios were 34.6 and 3.9, respectively, and the percentage of time the drug remained above the MIC for the 12-h dosing interval was 100%; the corresponding ratios in ELF were 120 and 16.1, respectively, and the percentage of time the drug remained above the MIC was 100%. The long plasma and intrapulmonary linezolid half-lives and the percentage of time spent above the MIC of 100% of the dosing interval provide a pharmacokinetic rationale for drug administration every 12 h and indicate that linezolid is likely to be an effective agent for the treatment of pulmonary infections.