bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal
aadD2
Encodes an Aminoglycoside Nucleotidyltransferase in
Bacillus clausii
Authors: Bozdogan Bülent , Galopin Sébastien , Gerbaud Guy , Courvalin Patrice , Leclercq Roland 
Published: March 2003

ABSTRACT

Bacillus clausii
SIN is one of the four strains of
B. clausii
composing a probiotic administered to humans for the prevention of gastrointestinal side effects due to oral antibiotic therapy. The strain is resistant to kanamycin, tobramycin, and amikacin. A gene conferring aminoglycoside resistance was cloned into
Escherichia coli
and sequenced. The gene, called
aadD2
, encoding a putative 246-amino acid protein, shared 47% identity with
ant(4
′
)-Ia
from
Staphylococcus aureus
, which encodes an aminoglycoside 4′-
O
-nucleotidyltransferase. Phosphocellulose paper-binding assays indicated that the gene product was responsible for nucleotidylation of kanamycin, tobramycin, and amikacin. The
aadD2
gene was detected by DNA-DNA hybridization in the three other strains of the probiotic mixture and in the reference strain
B. clausii
DSM8716, although it did not confer resistance in these strains. Mutations in the sequence of the putative promoter for
aadD2
from
B. clausii
SIN resulted in higher identity with consensus promoter sequences and may account for aminoglycoside resistance in that strain. The
aadD2
gene was chromosomally located in all strains and was not transferable by conjugation. These data indicate that chromosomal
aadD2
is specific to
B. clausii
.
Molecular Determination of Point Mutation Haplotypes in the Dihydrofolate Reductase and Dihydropteroate Synthase of
Plasmodium falciparum
in Three Districts of Northern Tanzania
Authors: Pearce Richard J. , Drakeley Chris , Chandramohan Daniel , Mosha Frank , Roper Cally 
Published: March 2003

ABSTRACT

The antimalarial combination of sulfadoxine and pyrimethamine (SP) was introduced as first-line treatment for uncomplicated malaria in Tanzania during 2001 following 18 years of second-line use. The genetic determinants of in vitro resistance to the two drugs individually are shown to be point mutations at seven sites in the dihydrofolate reductase gene (
dhfr
) conferring resistance to pyrimethamine and five sites in the dihydropteroate synthase (
dhps
) gene conferring resistance to sulfadoxine. Different combinations of mutations within each gene confer differing degrees of insensitivity, but information about the frequency with which allelic haplotypes occur has been lacking because of the complicating effects of multiple infection. Here we used a novel high-throughput sequence-specific oligonucleotide probe-based approach to examine the present resistance status of three
Plasmodium falciparum
populations in northern Tanzania. By using surveys of asymptomatic infections and screening for the presence of all known point mutations in
dhfr
and
dhps
genes, we showed that just five
dhfr
and three
dhps
allelic haplotypes are present. High frequencies of both triple-mutant
dhfr
and double-mutant
dhps
mutant alleles were found in addition to significant interregional heterogeneity in allele frequency. In vivo studies have shown that the cooccurrence of three
dhfr
mutations and two
dhps
mutations in an infection prior to treatment is statistically predictive of treatment failure. We have combined data for both loci to determine the frequency of two-locus genotypes. The triple-
dhfr
/double-
dhps
genotype is present in all three regions with frequencies ranging between 30 and 63%, indicating that treatment failure rates are likely to be high.
Pharmacokinetics and Efficacy of Linezolid in a Gerbil Model of
Streptococcus pneumoniae
-Induced Acute Otitis Media
Authors: Humphrey William R. , Shattuck Mark H. , Zielinski Raymond J. , Kuo Ming-Shang T. , Biermacher John J. , Smith Donald P. , Jensen Jana L. , Schaadt Ronda D. , Zurenko Gary E. , Richards Ivan M. 
Published: March 2003

ABSTRACT

The oxazolidinone linezolid represents a new antibacterial class of potential benefit in managing multidrug-resistant gram-positive infections, including those caused by
Streptococcus pneumoniae
. In a gerbil model of acute otitis media (AOM) induced by either penicillin-resistant
S. pneumoniae
(PRSP; amoxicillin MIC = 8 μg/ml, linezolid MIC = 1 μg/ml) or penicillin-susceptible
S. pneumoniae
(PSSP; amoxicillin MIC = 0.015 μg/ml, linezolid MIC = 1 μg/ml), we explored the plasma and ear fluid levels of linezolid required to demonstrate efficacy. Threshold pathogen doses required to induce bilateral AOM (1,500 CFU/ear with PRSP; 30 CFU/ear with PSSP) were administered to gerbils by intrabullar injection on day 0. At peak infection (∼10
6
to 10
7
CFU/ear flush; day 2 for PRSP-AOM and day 3 for PSSP-AOM), twice-a-day oral doses of linezolid, amoxicillin, or vehicle were administered over 4.5 days prior to collection and assay of middle ear effluents for
S. pneumoniae
content. Linezolid doses of ≥10 mg/kg of body weight induced significant cure rates of ≥72% versus both PRSP and PSSP infections, whereas amoxicillin at ≤100 mg/kg was consistently effective only versus PSSP-AOM. Plasma and ear fluid levels of linezolid necessary to elicit pneumococcal eradication from the middle ear were measured by high-performance liquid chromatography-tandem mass spectrometry and found to be similar both within and between each infection protocol. The plasma-ear fluid pharmacodynamic profile associated with linezolid efficacy was a
T
>MIC of ≥42%, a
C
max
/MIC ratio of ≥3.1, and a (24-h area under the curve)/MIC ratio of ≥30 h. Application of this model will be useful in defining preclinical pharmacodynamic relationships of novel antibiotics necessary to cure
S. pneumoniae
-induced AOM.
Stability of Colistin and Colistin Methanesulfonate in Aqueous Media and Plasma as Determined by High-Performance Liquid Chromatography
Authors: Li Jian , Milne Robert W. , Nation Roger L. , Turnidge John D. , Coulthard Kingsley 
Published: March 2003

ABSTRACT
The stabilities of colistin and colistin methanesulfonate (CMS) in different aqueous media were studied by specific high-performance liquid chromatography (HPLC) methods. Colistin was stable in water at 4 and 37°C for up to 60 days and 120 h, respectively. However, degradation was observed when colistin was stored in isotonic phosphate buffer (0.067 M, pH 7.4) and human plasma at 37°C. The stability of CMS from three different sources in water was explored by strong-anion-exchange (SAX) HPLC for CMS and by measuring the concentrations of colistin formed from the hydrolysis of CMS. The peaks of CMS in SAX HPLC disappeared almost completely after 12 h at 37°C, but appeared to remain intact for up to 2 days at 4°C. Over the same period, there was no formation of colistin at 4°C. In water, phosphate buffer, and plasma, there was rapid formation of colistin within 24 to 48 h at 37°C from the three sources of CMS. The hydrolysis products were assumed to be a complex mixture of many different sulfomethyl derivatives, including colistin. The stability of a fourth source of CMS in Mueller-Hinton broth examined during 30 min at 37°C revealed no formation of colistin. Along with previous microbiological studies, this suggested that different sulfomethyl CMSs possess intrinsic antibacterial activity. These results will be helpful for understanding the pharmacokinetics and pharmacodynamics of colistin and CMS in humans and animals.
MexXY-OprM Efflux Pump Is Necessary for Adaptive Resistance of
Pseudomonas aeruginosa
to Aminoglycosides
Authors: Hocquet Didier , Vogne Christelle , El Garch Farid , Vejux Anne , Gotoh Naomasa , Lee Angela , Lomovskaya Olga , Plésiat Patrick 
Published: March 2003

ABSTRACT

Exposure of
Pseudomonas aeruginosa
to aminoglycosides frequently selects for recalcitrant subpopulations exhibiting an unstable, “adaptive” resistance to these antibiotics. In this study, we investigated the implication in the phenomenon of MexXY-OprM, an active efflux system known to export aminoglycosides in
P. aeruginosa
. Immunoblotting experiments demonstrated that the transporter MexY, but not the outer membrane pore OprM, was overproduced during the post-drug exposure adaptation period in wild-type strain PAO1. Furthermore, MexY production was dependent upon the degree of bacterial exposure to gentamicin (drug concentration). In contrast to parental strain PAO1, mutants defective in MexXY or in OprM were unable to develop adaptive resistance. Altogether, these results indicate that the resistance process requires the rapid production of MexXY and the interaction of these proteins with the constitutively produced component OprM.
In Vitro Antifungal Activity of Micafungin (FK463) against Dimorphic Fungi: Comparison of Yeast-Like and Mycelial Forms
Authors: Nakai Toru , Uno Jun , Ikeda Fumiaki , Tawara Shuichi , Nishimura Kazuko , Miyaji Makoto 
Published: March 2003

ABSTRACT

The characteristics of in vitro micafungin (FK463) antifungal activity against six species of dimorphic fungi were investigated in accordance with the NCCLS M27-A microdilution methods. MICs of micafungin, amphotericin B, itraconazole, and fluconazole for
Histoplasma capsulatum
var.
capsulatum
,
Blastomyces dermatitidis
,
Paracoccidioides brasiliensis
,
Penicillium marneffei
, and
Sporothrix schenckii
were determined both for the yeast-like form and mycelial form.
Coccidioides immitis
was tested only in its mycelial form. We have clearly demonstrated that the in vitro activity of micafungin depends considerably on the growth form of dimorphic fungi. Micafungin exhibited potent activity against the mycelial forms of
H. capsulatum
,
B. dermatitidis
, and
C. immitis
(MIC range, 0.0078 to 0.0625 μg/ml), while it was very weakly active against their yeast-like forms (MIC range, 32 to >64 μg/ml). Micafungin was also more active against the mycelial forms than the yeast-like forms of
Paracoccidioides brasiliensis
,
Penicillium marneffei
, and
S. schenckii
. The MICs of amphotericin B were 2 to 5 dilutions lower for the mycelial forms than for the yeast-like forms of
B. dermatitidis
and
Paracoccidioides brasiliensis
. There was no apparent difference in the activity of itraconazole between the two forms. The MICs of fluconazole for the yeast-like forms were generally lower than those for the mycelial forms, and considerably so for
B. dermatitidis
. These results suggest that the growth form employed in antifungal susceptibility testing of dimorphic fungi can considerably influence the interpretation of results. At present, it cannot be judged whether micafungin has clinical usefulness for dimorphic fungus infections, since for most fungi it remains uncertain which growth form correlates better with therapeutic outcome. However, the results of this study warrant further investigations of micafungin as a therapeutic agent for infections caused by dimorphic fungi.
Epidemiology of Rifampin ADP-Ribosyltransferase (
arr-2
) and Metallo-β-Lactamase (
bla
IMP-4
) Gene Cassettes in Class 1 Integrons in
Acinetobacter
Strains Isolated from Blood Cultures in 1997 to 2000
Authors: Houang Elizabeth T. S. , Chu Yiu-Wai , Lo Wai-Sing , Chu Ka-Yi , Cheng Augustine F. B. 
Published: March 2003

ABSTRACT

We characterized two new gene cassettes in an
Acinetobacter
isolate: one harbored the metallo-β-lactamase (IMP-4) gene
bla
IMP-4
, the other harbored the rifampin ADP-ribosyltransferase (ARR-2) gene
arr-2
, and both arrayed with the aminoglycoside acetyltransferase [AAC(6′)-Ib
7
] gene cassette
aacA4
in two separate class 1 integrons. The epidemiology of these gene cassettes in isolates from blood cultures obtained from 1997 to 2000 was studied. Isolates bearing either the
bla
IMP-4
or the
arr-2
gene cassette or both represented 17.5% (10 of 57) of isolates in 1997, 16.1% (10 of 62) in 1998, 2.5% (1 of 40) in 1999, and 0% (0 of 58) in 2000. These two gene cassettes, probably borne on two separate integrons, were found in at least three genomic DNA groups, with evidence of clonal dissemination in the intensive care unit during 1997 to 1998. Seventeen of the 52
Acinetobacter baumannii
(genomic DNA group 2) isolates from 1997 to 2000 harbored
intI1
, but only one was positive for these gene cassettes, whereas 20 of the 21
intI1
-positive isolates of all other genomic DNA groups were positive for either or both of them. Reduced susceptibility to imipenem and rifampin was seen only in isolates harboring the
bla
IMP-4
and
arr-2
cassettes, respectively. The aminoglycoside phosphotransferase [APH(3′)-VIa] gene
aph(3′)-VIa
was detected in all 21 isolates for which the MIC of amikacin was ≥8 μg/ml, with or without
aacA4
, whereas
aacA4
alone was found in isolates for which the MIC of amikacin was 0.5 to 2 μg/ml. Significant differences between the 17
intI1
-positive and 47
intI1
-negative isolates belonging to genomic DNA group 3 from 1997 to 1998 in the MICs of amikacin, gentamicin, imipenem, sulfamethoxazole, and ceftazidime were observed (Mann-Whitney test,
P
< 0.001 to 0.01).
In Vitro Activities of Piperaquine and Other 4-Aminoquinolines against Clinical Isolates ofPlasmodium falciparumin Cameroon
Authors: Basco Leonardo K. , Ringwald Pascal 
Published: March 2003

ABSTRACTThe spread of chloroquine-resistantPlasmodium falciparumcalls for a constant search for new drugs. The in vitro activity of piperaquine, a new Chinese synthetic drug belonging to the bisquinolines, was evaluated in 103 fresh clinical isolates ofP. falciparumin Cameroon, Central Africa, and compared with that of other 4-aminoquinoline and Mannich base derivatives and dihydroartemisinin. Piperaquine was highly active (geometric mean 50% inhibitory concentration, 38.9 nmol/liter; range, 7.76 to 78.3 nmol/liter) and equally active (P> 0.05) against the chloroquine-sensitive and the chloroquine-resistant isolates. There was a significant but low correlation of response between chloroquine and piperaquine (r= 0.257,P< 0.05). These results suggest that further development of piperaquine, in combination with dihydroartemisinin, holds promise for use in chloroquine-resistant regions of endemicity.
Pharmacokinetics and Metabolism of [14C]Ribavirin in Rats and Cynomolgus Monkeys
Authors: Lin Chin-Chung , Yeh Li-Tain , Luu Trong , Lourenco David , Lau Johnson Y. N. 
Published: March 2003

ABSTRACTAbsorption, pharmacokinetics, distribution, metabolism, and excretion of [14C]ribavirin were studied in rats (30 mg/kg of body weight) and cynomolgus monkeys (10 mg/kg) after intravenous (i.v.) and oral administration. The oral absorption and bioavailability were 83 and 59%, respectively, in rats and 87 and 55%, respectively, in monkeys. After i.v. administration, the elimination half-life (t[1/2]) was 9.9 h in rats and 130 h in monkeys and the total body clearance was 2,600 ml/h/kg in rats and 224 ml/h/kg in monkeys. The apparent volume of distribution was 11.4 liter/kg in rats and 29.4 liter/kg in monkeys. There was extensive distribution of drug-derived radioactivity into red blood cells and extensive metabolism of ribavirin in rats and a lesser degree of metabolism in monkeys. Excretion of total radioactivity in urine from rats accounted for 84% of the i.v. dose and 83% of the oral dose, whereas that from monkeys accounted for 47% of the i.v. dose and 67% of the oral dose. Several metabolites were observed in plasma and urine from both species. The amount of unchanged ribavirin in urine from both species was quite small after either i.v. or oral administration.
Time-Kill Studies of the Antianaerobe Activity of Garenoxacin Compared with Those of Nine Other Agents
Authors: Credito Kim L. , Jacobs Michael R. , Appelbaum Peter C. 
Published: March 2003

ABSTRACT
The activities of garenoxacin, ciprofloxacin, levofloxacin, moxifloxacin, trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 20 anaerobes were tested. At two times the MIC, garenoxacin was bactericidal against 19 of 20 strains after 48 h and against 17 of 20 after 24 h. Other drugs, except clindamycin (which gave lower killing rates), gave killing rates similar to those for garenoxacin.
Activities of ABT-773 against
Listeria monocytogenes
and Coryneform Bacteria of Clinical Interest
Authors: Conejo María del Carmen , Martínez-Martínez Luis , Pascual Álvaro , Suárez Ana Isabel , Perea Evelio J. 
Published: March 2003

ABSTRACT

The in vitro activities of ABT-773 were evaluated against 15
Listeria monocytogenes
strains and 196 coryneform bacteria isolated from clinical samples. One hundred percent of the
L. monocytogenes
strains were inhibited by ≤0.015 μg of ABT-773/ml. MICs of ABT-773 (μg/ml) at which 50% of the isolates tested were inhibited (MIC
50
s) and MIC
90
s for other organisms were 0.125 and 0.5 (
Corynebacterium amycolatum
), 1 and >32 (
Corynebacterium jeikeium
), 0.03 and >32 (
Corynebacterium minutissimum
), >32 and >32 (
Corynebacterium pseudodiphtheriticum
and
Corynebacterium urealyticum
), 0.125 and >32 (
Corynebacterium striatum
), and 0.03 and 0.5 (
Rhodococcus equi
), respectively.
In Vitro Metronidazole and Tinidazole Activities against Metronidazole- Resistant Strains of
Trichomonas vaginalis
Authors: Crowell Andrea L. , Sanders-Lewis Kolby A. , Secor W. Evan 
Published: March 2003

ABSTRACT

The in vitro activities of tinidazole and metronidazole against
Trichomonas vaginalis
isolates clinically resistant to metronidazole were compared. Minimal lethal concentrations (MLCs) of tinidazole were significantly lower than MLCs of metronidazole. Increased metronidazole resistance correlated with increased tinidazole resistance. These data support a role for tinidazole in the treatment of trichomoniasis.
Activity of and Resistance to Moxifloxacin in
Staphylococcus aureus
Authors: Ince Dilek , Zhang Xiamei , Hooper David C. 
Published: March 2003

ABSTRACT

Moxifloxacin has enhanced potency against
Staphylococcus aureus
, lower propensity to select for resistant mutants, and higher bactericidal activity against highly resistant strains than ciprofloxacin. Despite similar activity against purified
S. aureus
topoisomerase IV and DNA gyrase, it selects for topoisomerase IV mutants, making topoisomerase IV the preferred target in vivo.
In Vitro Synergy of Caspofungin and Itraconazole against
Aspergillus
spp.: MIC versus Minimal Effective Concentration End Points
Authors: Shalit Itamar , Shadkchan Yona , Samra Zmira , Osherov Nir 
Published: March 2003

ABSTRACT

Caspofungin and itraconazole were studied alone and in combination against 31 clinical isolates of
Aspergillus
spp. according to NCCLS M38-P guidelines. MICs and microscopic minimal effective concentrations (MECs) were recorded, and synergy was calculated by using both end points. Synergy or synergy to additivity was found in 30 of 31 isolates by using MIC end points. With MEC end points no synergy was found and indifference was detected in 26 of 31 strains.
Genetic Characterization of Fluoroquinolone-Resistant
Streptococcus pneumoniae
Strains Isolated during Ciprofloxacin Therapy from a Patient with Bronchiectasis
Authors: de la Campa Adela G. , Ferrandiz María-José , Tubau Fe , Pallarés Román , Manresa Federico , Liñares Josefina 
Published: March 2003

ABSTRACT

Five Spain
9V-3
Streptococcus pneumoniae
strains were isolated from a patient with bronchiectasis who had received long-term ciprofloxacin therapy. One ciprofloxacin-susceptible strain was isolated before treatment, and four ciprofloxacin-resistant strains were isolated during treatment. The resistant strains were derived from the susceptible strain either by a
parC
mutation (low-level resistance) or by
parC
and
gyrA
mutations (high-level resistance). This study shows that ciprofloxacin therapy in a patient colonized by susceptible
S. pneumoniae
may select fluoroquinolone-resistant mutants.
Multiplex PCR for Detection of Aminoglycoside Resistance Genes in Enterococci
Authors: Vakulenko Sergei B. , Donabedian Susan M. , Voskresenskiy Anatoliy M. , Zervos Marcus J. , Lerner Stephen A. , Chow Joseph W. 
Published: March 2003

ABSTRACT

A multiplex PCR procedure for detecting the aminoglycoside resistance genes
aac(6′)-Ie-aph(2")-Ia
,
aph(2")-Ib
,
aph(2")-Ic
,
aph(2")-Id
,
aph(3′)-IIIa
, and
ant(4′)-Ia
was evaluated and found to determine accurately the presence of these genes in enterococci.
Integron-Associated Antibiotic Resistance in
Salmonella enterica
Serovar Typhi from Asia
Authors: Ploy Marie-Cécile , Chainier Delphine , Tran Thi Nhu Hoa , Poilane Isabelle , Cruaud Philippe , Denis François , Collignon Anne , Lambert Thierry 
Published: March 2003

ABSTRACT

Eighteen of 25 isolates of
Salmonella enterica
serovar Typhi were multidrug resistant and contained class 1 integrons with a single cassette,
dfrVII
or
aadA1
. The
dfrVII
-containing integron was likely borne on an IncHI1 plasmid.
Salmonella
serovar Typhi could become resistant to broad-spectrum cephalosporins by integrating cassettes, such as
veb-1
, a common cassette in Asia.
Novel Tetracycline Resistance Determinant from the Oral Metagenome
Authors: Diaz-Torres M. L. , McNab R. , Spratt D. A. , Villedieu A. , Hunt N. , Wilson M. , Mullany P. 
Published: March 2003

ABSTRACT

A major drawback of most studies on how bacteria become resistant to antibiotics is that they concentrate mainly on bacteria that can be cultivated in the laboratory. In the present study, we cloned part of the oral metagenome and isolated a novel tetracycline resistance gene,
tet
(37), which inactivates tetracycline.
Molecular Characterization and Antimicrobial Susceptibility of Fluoroquinolone-Resistant or -Susceptible
Streptococcus pneumoniae
from Hong Kong
Authors: Morrissey Ian , Farrell David J. , Bakker Sarah , Buckridge Sylvie , Felmingham David 
Published: March 2003

ABSTRACT

Fluoroquinolone resistance in
Streptococcus pneumoniae
isolated from Hong Kong as part of Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin 1999/2000 was found to be due to the spread of the Spain
23F
-1 clone (mainly a Spain
23F
-1-14 variant). All the isolates were multidrug resistant but were susceptible to quinupristin-dalfopristin, linezolid, and telithromycin. The Spain
23F
-1 clone also occurred among antimicrobial-susceptible isolates, which suggests that the primary source of this clone may have been Asia rather than Iberia.
Activity of Posaconazole against
Pseudallescheria boydii
: In Vitro and In Vivo Assays
Authors: González Gloria M. , Tijerina Rolando , Najvar Laura K. , Bocanegra Rosie , Rinaldi Michael G. , Loebenberg David , Graybill John R. 
Published: March 2003

ABSTRACT

Thirty isolates of
Pseudallescheria boydii
were tested to compare the in vitro activity of posaconazole with those of fluconazole and itraconazole, using NCCLS methods. Posaconazole was evaluated in an immunosuppressed mouse model of disseminated pseudallescheriasis. Posaconazole was more effective than itraconazole and as effective as fluconazole in preventing death and significantly reducing the CFU of
P. boydii
from tissues.
Tissue Penetration by Ertapenem, a Parenteral Carbapenem Administered Once Daily, in Suction-Induced Skin Blister Fluid in Healthy Young Volunteers
Authors: Laethem T. , De Lepeleire I. , McCrea J. , Zhang J. , Majumdar A. , Musson D. , Rogers D. , Li S. , Guillaume M. , Parneix-Spake A. , Deutsch P. 
Published: March 2003

ABSTRACT

The penetration of 1 g of intravenous ertapenem once daily for 3 days in suction-induced skin blisters was evaluated. Ten forearm blisters were formed (
n
= 12) 12 h prior to the last dose. Concentrations of ertapenem in blister fluid exceeded 4 μg/ml (the MIC at which 90% of the isolates tested are eliminated) for the entire dosing interval. The area under the concentration-time curve for 0 to 24 h ratio of blister fluid to plasma was 61% (90% confidence interval, 56, 65%) suggesting good blister penetration.