bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACI-1 from
Acidaminococcus fermentans
: Characterization of the First β-Lactamase in Anaerobic Cocci
Authors: Galán J. C. , Reig M. , Navas A. , Baquero F. , Blázquez J. 
Published: July 2002

ABSTRACT

Acidaminococcus fermentans
belongs to the group of strictly anaerobic gram-negative cocci. All previously described
Acidaminococcus
strains are susceptible to β-lactam antibiotics. An
A. fermentans
strain (RYC-MR95) resistant to penicillin and expanded-spectrum cephalosporin (amoxicillin and cefotaxime MICs, 64 μg/ml) was isolated from a human perianal abscess. A fragment encoding a β-lactamase from genomic DNA was cloned in
Escherichia coli
K-12 strain HB101, and the recombinant strain expressed resistance to amoxicillin (MIC, 1,024 μg/ml) and cefotaxime (MIC, 4 μg/ml). Clavulanic acid decreased the MICs to 8 and 0.03 μg/ml, respectively. Analysis of the nucleotide sequence revealed a new class A β-lactamase, ACI-1. In accordance with its biochemical properties, we propose to assign ACI-1 to functional group 2be. The ACI-1 enzyme (estimated pI 4.3) had <50% amino acid identity with any other class A β-lactamases, the closest being ROB-1 from
Haemophilus influenzae
(44%). ACI-1 was closer to class A β-lactamases from some gram-positive organisms (41 to 44% amino acid identity with
Bacillus
β-lactamases) than to most class A enzymes from gram-negative organisms (TEM-1, 24.6%). The
aci1
gene had a G+C content of 42.1%, in contrast with 56% G+C content for genomic DNA from
A. fermentans
, thus suggesting that
aci1
may have been obtained by horizontal gene transfer.
In Vitro Susceptibilities of
Capnocytophaga
Isolates to β-Lactam Antibiotics and β-Lactamase Inhibitors
Authors: Jolivet-Gougeon Anne , Buffet Anne , Dupuy Cécile , Sixou Jean-Louis , Bonnaure-Mallet Martine , David Sandrine , Cormier Michel 
Published: July 2002

ABSTRACT

The susceptibilities of 43 pharyngeal isolates of
Capnocytophaga
to beta-lactam antibiotics, alone or in combination with beta-lactamase inhibitors, were tested by an agar dilution method. The 34 beta-lactamase-positive strains were highly resistant to beta-lactams, but the intrinsic activities of clavulanate, tazobactam, and sulbactam against
Capnocytophaga
, even beta-lactamase producers, indicates that these beta-lactamase inhibitors could be used for empirical treatment of neutropenic patients with oral sources of infection.
Comparative In Vitro Activities of Daptomycin and Vancomycin against Resistant Gram-Positive Pathogens
Authors: Snydman D. R. , Jacobus N. V. , McDermott L. A. , Lonks J. R. , Boyce J. M. 
Published: July 2002

ABSTRACT

The in vitro activity of daptomycin against 224 current gram-positive clinical isolates including vancomycin-resistant
Enterococcus faecium
(VREF), methicillin-resistant
Staphylococcus aureus
(MRSA), methicillin-resistant
Staphylococcus
spp. (MRSS), and penicillin-resistant
Streptococcus pneumoniae
(PRSP) was evaluated. The MICs at which 90% of isolates are inhibited for daptomycin and vancomycin, respectively, were as follows: MRSA, 1 and 2 μg/ml; MRSS, 1 and 4 μg/ml; PRSP, 1 and 0.5 μg/ml; and VREF, 2 and >64 μg/ml. Daptomycin was bactericidal against 82% of 17 VREF isolates. The antibacterial activity of daptomycin was strongly dependent on the calcium concentration of the medium. Daptomycin was active against all gram-positive cocci tested.
Molecular Genetic Analysis of Nucleotide Polymorphisms Associated with Ethambutol Resistance in Human Isolates of
Mycobacterium tuberculosis
Authors: Ramaswamy Srinivas V. , Amin Amol G. , Göksel Servet , Stager Charles E. , Dou Shu-Jun , El Sahly Hana , Moghazeh Soraya L. , Kreiswirth Barry N. , Musser James M. 
Published: July 2002

ABSTRACT

Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB-susceptible
Mycobacterium tuberculosis
strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance-associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB-resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance-associated mutations in a single gene had nucleotide changes in
embB
, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of
M. tuberculosis
to EMB in vitro, including genes in the
iniA
operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype.
In Vitro Activities of Ketoconazole, Econazole, Miconazole, and
Melaleuca alternifolia
(Tea Tree) Oil against
Malassezia
Species
Authors: Hammer K. A. , Carson C. F. , Riley T. V. 
Published: July 2002

ABSTRACT

The in vitro activities of ketoconazole, econazole, miconazole, and tea tree oil against 54
Malassezia
isolates were determined by agar and broth dilution methods. Ketoconazole was more active than both econazole and miconazole, which showed very similar activities.
M. furfur
was the least susceptible species.
M. sympodialis
,
M. slooffiae
,
M. globosa
, and
M. obtusa
showed similar susceptibilities to the four agents.
Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in Treatment of Severe Pulmonary Aspergillosis in Leukopenic Rats
Authors: Van Etten Els W. M. , Stearne-Cullen Lorna E. T. , Ten Kate Marian T. , Bakker-Woudenberg Irma A. J. M. 
Published: July 2002

ABSTRACT

The therapeutic efficacy of long-circulating polyethylene glycol-coated liposomal amphotericin B (AMB) (PEG-AMB-LIP) was compared with that of AMB desoxycholate (Fungizone) in a model of severe invasive pulmonary aspergillosis in persistently leukopenic rats as well as in temporarily leukopenic rats. PEG-AMB-LIP treatment (intravenous administration) consisted of a single, or double (every 72 h), or triple (every 72 h) dose of 10 mg of AMB/kg of body weight, a double dose (every 72 h) of 14 mg of AMB/kg, or a 5-day treatment (every 24 h) with 6 mg/kg/dose. AMB desoxycholate was administered for 10 consecutive days at 1 mg of AMB/kg/dose. Treatment was started 30 h after fungal inoculation, at which time mycelial growth was firmly established. Both persistently and temporarily leukopenic rats died between 4 and 9 days after
Aspergillus fumigatus
inoculation when they were left untreated or after treatment with a placebo. In persistently leukopenic rats, a single dose of PEG-AMB-LIP (10 mg/kg) was as effective as the 10-day treatment with AMB desoxycholate (at 1 mg/kg/dose) in significantly prolonging the survival of rats infected with
A. fumigatus
and in reducing the dissemination of
A. fumigatus
to the liver. Prolongation of PEG-AMB-LIP treatment (double or triple dose or 5-day treatment) did not further improve efficacy. For temporarily leukopenic rats no major advances in efficacy were achieved compared to those for persistently leukopenic rats, probably because the leukocyte numbers in blood were restored too late in the course of infection.
Flow Cytometric Monitoring of Antibiotic-Induced Injury in
Escherichia coli
Using Cell-Impermeant Fluorescent Probes
Authors: Mortimer Fiona C. , Mason David J. , Gant Vanya A. 
Published: July 2002

ABSTRACT

Three fluorescent nucleic acid binding dyes—propidium iodide, TO-PRO-1, and SYTOX green—were evaluated, and their abilities to distinguish between bacterial cells with and without an intact cytoplasmic membrane were compared. Each dye was readily able to discriminate between healthy and permeabilized cells of
Escherichia coli
, although SYTOX green showed a greater enhancement in fluorescence intensity on staining-compromised, as opposed to healthy, cells in log-phase growth, than either PI or TO-PRO-1. Flow cytometric analysis of
E. coli
stained with these dyes after exposing them to several antimicrobial agents showed that all three dyes were able to detect antimicrobial action. Notably, however, the intensity of the cell-associated fluorescence was related to the mechanism of action of the antimicrobial agent. Large changes in fluorescence intensity were observed for all the dyes subsequent to β-lactam antibiotic action, but smaller changes (or no change) were seen subsequent to exposure to antimicrobials acting directly or indirectly on nucleic acid synthesis. Furthermore, cell-associated fluorescence did not relate to loss of viability as determined by plate counts. Despite offering much insight into antimicrobial mechanisms of action, these fundamental problems become relevant to the development of rapid antimicrobial susceptibility tests if colony formation is used as the standard.
Pharmacokinetics of an Everninomicin (SCH 27899) in Mice, Rats, Rabbits, and Cynomolgus Monkeys following Intravenous Administration
Authors: Lin C. , Gupta S. , Loebenberg D. , Cayen M. N. 
Published: July 2002

ABSTRACT

The pharmacokinetics of SCH 27899, a novel oligosaccharide compound of the everninomicin class with excellent activity against gram-positive strains, was studied with mice, rats, rabbits, and cynomolgus monkeys following intravenous administration as SCH 27899–
N
-methylglucamine–hydroxypropyl β-cyclodextrin. Concentrations of SCH 27899 in mouse serum, rat plasma, and rabbit serum were determined by a high-pressure liquid chromatography method on a poly(styrene-divinyl benzene) column, and those in monkey plasma were determined by a paired-ion chromatographic method. Plasma and serum concentrations of SCH 27899 exhibited a biexponential decline in all species following intravenous administration. The half-lives at β phase were 3.0 to 7.9 h in mice, rats, and rabbits and 24 h in cynomolgus monkeys. There was a linear relationship between the area under the curve extrapolated to infinity [AUC(I)] in mice and dose. Rabbits also exhibited dose proportionality in AUC(I). However, in rats, increasing the dose from 3 to 60 mg/kg of body weight resulted in a 49-fold increase in AUC(I). When the species was changed from mouse to rat, rabbit, or cynomolgus monkey, AUC(I) increased, whereas clearance (CL) decreased. It was concluded that the pharmacokinetics of SCH 27899 in animals varied with species; CL was the highest in mice and rats, followed by rabbits and cynomolgus monkeys.
Direct Measurement of the Anti-Influenza Agent Zanamivir in the Respiratory Tract following Inhalation
Authors: Peng Amy W. , Milleri Stefano , Stein Daniel S. 
Published: July 2002

ABSTRACT
In a single-center, randomized study, zanamivir (Relenza) concentrations in induced sputum samples and nasal washings of healthy adults following oral inhalation were measured. Concentrations in sputum exceeded the median viral neuraminidase 50% inhibitory concentration at 6, 12, and 24 h, and those in nasal washings did so at 6 and 12 h. There were no zanamivir-related adverse events or laboratory abnormalities.
Characterization of a Fish Antimicrobial Peptide: Gene Expression, Subcellular Localization, and Spectrum of Activity
Authors: Cole Alexander M. , Darouiche Rabih O. , Legarda Diana , Connell Nancy , Diamond Gill 
Published: July 2002

ABSTRACTAntimicrobial peptides are proposed to act as the first line of mucosal host defense by exerting broad-spectrum microbicidal activity against pathogenic microbes. Pleurocidin, a new 25-residue linear antimicrobial peptide, was recently isolated from the skin secretions of winter flounder (Pleuronectes americanus). The present study identifies the cDNA and gene encoding pleurocidin. The pleurocidin gene comprises four exons. Its upstream region demonstrates consensus binding sequences for transcription factors found in host defense genes in mammals, including sequences identical to the NF-IL6 and alpha and gamma interferon response elements. Pleurocidin is predicted to exist as a 68-residue prepropeptide that undergoes proteolytic cleavage of its amino-terminal signal and carboxy-terminal anionic propiece to form the active, mature peptide. Transmission electron microscopy localized pleurocidin to the mucin granules of skin and intestinal goblet cells. Significant synergy was shown to occur between pleurocidin andd-cycloserine targetingMycobacterium smegmatis. Pleurocidin was functionally active at physiologic concentrations of magnesium and calcium; however, high concentrations of these divalent cations ablated pleurocidin's activity against a standard test strain,Escherichia coliD31. Pleurocidin was tested against bacterial and fungal clinical isolates and showed broad-spectrum antimicrobial activity. Together, these data support the hypothesis that pleurocidin participates in innate mucosal immunity, and it may prove to be a beneficial therapeutic agent.
Enhanced Reduction of
Helicobacter pylori
Load in Precolonized Mice Treated with Combined Famotidine and Urease-Binding Polysaccharides
Authors: Icatlo Faustino C. , Kimura Nobutake , Goshima Hideo , Kodama Yoshikatsu 
Published: July 2002

ABSTRACT

The present study investigated the effect of a model urease-binding polysaccharide in combination with a histamine H
2
receptor antagonist on
Helicobacter pylori
colonization in vivo. Euthymic hairless mice were treated daily with dextran sulfate via drinking water and/or famotidine via intragastric gavage starting at 1 week postchallenge with a CagA
+
VacA
+
(type 1) strain of
H. pylori
. Treatment of precolonized mice for 2 weeks with dextran sulfate combined with famotidine yielded a group mean bacterial load (per 100 mg of gastric tissue) of log
10
1.04 CFU, which was significantly lower than those of the famotidine (log
10
3.35 CFU,
P
< 0.01) and dextran sulfate (log
10
2.45 CFU,
P
< 0.05) monotherapy groups and the infected nontreated group (log
10
3.64 CFU,
P
< 0.01). Eradication was achieved after 2 weeks of treatment in 50% or more of the test mice using drug combinations (1 or 2 weeks of famotidine plus 2 weeks of dextran sulfate) versus none in the monotherapy and positive control groups. The enhanced activity of the drug combination may be related to the daily pattern of transient acid suppression by famotidine inducing periodic bacterial convergence to superficial mucus sites penetrated by dextran sulfate from the lumen. Increased urease-dextran sulfate avidity was observed in vitro in the presence of famotidine and may partly account for the enhanced activity. With potential utility in abbreviating treatment time and eradication of antibiotic-resistant strains, the use of urease-targeted polysaccharides concurrently with a gastric acid inhibitor warrants consideration as an additional component of the standard multidrug chemotherapy of
H. pylori
infection.
Identification of the Conjugative
mef
Gene in Clinical
Acinetobacter junii
and
Neisseria gonorrhoeae
Isolates
Authors: Luna Vicki A. , Cousin Sydney , Whittington William L. H. , Roberts Marilyn C. 
Published: July 2002

ABSTRACT

The
mef
gene, originally described for gram-positive organisms and coding for an efflux pump, has been identified in clinical isolates of
Acinetobacter junii
and
Neisseria gonorrhoeae
. These strains could transfer the
mef
gene at frequencies ranging from 10
−6
to 10
−9
into one or more of the following recipients: gram-negative
Moraxella catarrhalis
,
Neisseria perflava/sicca
and
Neisseria mucosa
and gram-positive
Enterococcus faecalis
. Three
Streptococcus pneumoniae
strains could transfer the
mef
gene into
Eikenella corrodens
,
Haemophilus influenzae
,
Kingella denitrificans
,
M. catarrhalis
,
Neisseria meningitidis
,
N. perflava/sicca
, and
N. mucosa
at similar frequencies. The
mef
gene can thus be transferred to and expressed in a variety of gram-negative recipients.
Phase I/II Trial of the Pharmacokinetics, Safety, and Antiretroviral Activity of Tenofovir Disoproxil Fumarate in Human Immunodeficiency Virus-Infected Adults
Authors: Barditch-Crovo Patricia , Deeks Steven G. , Collier Ann , Safrin Sharon , Coakley Dion F. , Miller Michael , Kearney Brian P. , Coleman Rebecca L. , Lamy Patrick D. , Kahn James O. , McGowan Ian , Lietman Paul S. 
Published: July 2002

ABSTRACTTenofovir DF is an antiviral nucleotide with activity against human immunodeficiency virus type 1 (HIV-1). The pharmacokinetics, safety, and activity of oral tenofovir DF in HIV-1-infected adults were evaluated in a randomized, double-blind, placebo-controlled, escalating-dose study of four doses (75, 150, 300, and 600 mg given once daily). Subjects received a single dose of tenofovir DF or a placebo, followed by a 7-day washout period. Thereafter, subjects received their assigned study drug once daily for 28 days. Pharmacokinetic parameters were dose proportional and demonstrated no change with repeated dosing. Reductions in plasma HIV-1 RNA were dose related at tenofovir DF doses of 75 to 300 mg, but there was no increase in virus suppression between the 300- and 600-mg dose cohorts, despite dose-proportional increases in drug exposure. Grade III or IV adverse events were limited to laboratory abnormalities, including elevated creatine phosphokinase and liver function tests, which resolved with or without drug discontinuation and without sequelae. No patients developed detectable sequence changes in the reverse transcriptase gene.
Molecular Analysis of Tetracycline Resistance in
Pasteurella aerogenes
Authors: Kehrenberg Corinna , Schwarz Stefan 
Published: July 2002

ABSTRACT

Tetracycline-resistant
Pasteurella aerogenes
isolates obtained from the intestinal tract of swine were investigated for their
tet
genes by PCR analysis and hybridization experiments. In contrast to
Pasteurella
isolates from the respiratory tract,
tet
(H) genes were detected in the chromosomal DNA of only 2 of the 24 isolates, one of which also carried two copies of a
tet
(B) gene. All other
P. aerogenes
isolates carried
tet
(B) genes, which are the predominant
tet
genes among
Enterobacteriaceae
. A single isolate harbored a
tet
(B) gene as part of a truncated Tn
10
element on the 4.8-kb plasmid pPAT2. Comparative analysis of the pPAT2 sequence suggested that the Tn
10
relic on plasmid pPAT2 is the result of several illegitimate recombination events. The remaining 21
P. aerogenes
isolates carried one or two copies of the
tet
(B) gene in their chromosomal DNA. In the majority of the cases, these
tet
(B) genes were associated with copies of Tn
10
as confirmed by their
Sfu
I and
Bam
HI hybridization patterns. No correlation between the number of
tet
gene copies and the MICs of tetracycline, doxycyline and minocycline was observed.
Mechanism of Action of the Des-F(6) Quinolone BMS-284756 Measured by Supercoiling Inhibition and Cleavable Complex Assays
Authors: Wu Ping , Lawrence Laura E. , Denbleyker Kenneth L. , Barrett John F. 
Published: July 2002

ABSTRACT

BMS-284756 (T-3811ME), a novel des-F(6) quinolone, was tested in the supercoiling inhibition and cleavable complex assays against
Escherichia coli
DNA gyrase, a target of quinolones. The results suggest that BMS-284756 has the same mechanism of action against DNA gyrase as other quinolones and a similar level of potency.
Germinated and Nongerminated Conidial Suspensions for Testing of Susceptibilities of
Aspergillus
spp. to Amphotericin B, Itraconazole, Posaconazole, Ravuconazole, and Voriconazole
Authors: Espinel-Ingroff A. 
Published: July 2002

ABSTRACT

The effect of germinated and nongerminated conidia of
Aspergillus
spp. on the fungistatic (National Committee for Clinical Laboratory Standards document M38-P) and fungicidal activities (MICs and minimal fungicidal concentrations [MFCs] respectively) of amphotericin B, itraconazole, posaconazole (SCH56592), ravuconazole (BMS-207147), and voriconazole was evaluated. MFCs were the lowest drug dilutions that showed fewer than three colonies (99.9% killing). Overall, the MICs (0.12 to 4 μg/ml) and MFCs (0.5 to >8 μg/ml) of all of the agents tested with both inocula were the same or within 2 dilutions for the 72 isolates. Therefore, MICs and MFCs can be obtained with convenient and standardized nongerminated conidia.
Activities of Linezolid against Rapidly Growing Mycobacteria
Authors: Wallace R. J. , Brown-Elliott B. A. , Ward S. C. , Crist C. J. , Mann L. B. , Wilson R. W. 
Published: July 2002

ABSTRACTLinezolid is an oxazolidinone available as an oral drug which has activity against most gram-positive bacteria. However, few species of the genusMycobacteriumhave been studied. We tested 249 clinical isolates and 10 reference strains of rapidly growing mycobacteria for susceptibility to linezolid by broth microdilution. Clinical species included theMycobacterium fortuitumgroup (n= 74),M. abscessus(n= 98),M. chelonae(n= 50),M. mucogenicum(n= 10), andM. fortuitumthird biovariant complex (10). The modal MIC forM. mucogenicumwas 1.0 μg/ml, and the MIC at which 90% of the isolates tested are inhibited (MIC90) was 4 μg/ml; the modal MIC for theM. fortuitumgroup was 4 μg/ml, and the MIC90was 16 μg/ml; the modal MIC for theM. fortuitumthird biovariant complex was 4 μg/ml, and the MIC90was 8 μg/ml; the modal MIC forM. chelonaewas 8 μg/ml, and the MIC90was 16 μg/ml; and the modal MIC forM. abscessuswas 32 μg/ml, and the MIC90was 64 μg/ml. Based on peak levels of linezolid in serum of 15 to 20 μg/ml, we propose the following broth MIC breakpoints for these species: susceptible, ≤ 8 μg/ml; moderately susceptible, 16 μg/ml; and resistant, ≥32 μg/ml). These studies demonstrate the excellent potential of linezolid for therapy of rapidly growing mycobacteria.
In Vitro and In Vivo Properties of Ro 63-9141, a Novel Broad-Spectrum Cephalosporin with Activity against Methicillin-Resistant Staphylococci
Authors: Hebeisen Paul , Heinze-Krauss Ingrid , Angehrn Peter , Hohl Peter , Page Malcolm G. P. , Then Rudolf L. 
Published: July 2002

ABSTRACT

Ro 63-9141 is a new member of the pyrrolidinone-3-ylidenemethyl cephem series of cephalosporins. Its antibacterial spectrum was evaluated against significant gram-positive and gram-negative pathogens in comparison with those of reference drugs, including cefotaxime, cefepime, meropenem, and ciprofloxacin. Ro 63-9141 showed high antibacterial in vitro activity against gram-positive bacteria except ampicillin-resistant enterococci, particularly vancomycin-resistant strains of
Enterococcus faecium
. Its MIC at which 90% of the isolates tested were inhibited (MIC
90
) for methicillin-resistant
Staphylococcus aureus
(MRSA) was 4 μg/ml. Ro 63-9141 was bactericidal against MRSA. Development of resistance to the new compound in MRSA was not observed. Ro 63-9141 was more potent than cefotaxime against penicillin-resistant
Streptococcus pneumoniae
(MIC
90
= 2 μg/ml). It was active against ceftazidime-susceptible strains of
Pseudomonas aeruginosa
and against
Enterobacteriaceae
except
Proteus vulgaris
and some isolates producing extended-spectrum β-lactamases. The basis for the antibacterial spectrum of Ro 63-9141 lies in its affinity to essential penicillin-binding proteins, including PBP 2′ of MRSA, and its stability towards β-lactamases. The in vivo findings were in accordance with the in vitro susceptibilities of the pathogens. These data suggest the potential utility of Ro 63-9141 for the therapy of infections caused by susceptible pathogens, including MRSA. Since insufficient solubility of Ro 63-9141 itself precludes parenteral administration in humans, a water-soluble prodrug, Ro 65-5788, is considered for development.