bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Antimicrobial Properties of Recombinant ASABF, an Antimicrobial Peptide Isolated from the Nematode
Ascaris suum
Authors: Zhang Hong , Yoshida Shigenobu , Aizawa Tomoyasu , Murakami Ritsuko , Suzuki Masato , Koganezawa Nozomu , Matsuura Atsushi , Miyazawa Mitsuhiro , Kawano Keiichi , Nitta Katsutoshi , Kato Yusuke 
Published: July 2002

ABSTRACT

ASABF is a CSαβ-type antimicrobial peptide that contains four intramolecular disulfide bridges (Y. Kato and S. Komatsu, J. Biol. Chem. 271:30493–30498, 1996). In the present study, a recombinant ASABF was produced by using a yeast expression system, and its antimicrobial activity was characterized in detail. The recombinant ASABF was active against all gram-positive bacteria tested (7 of 7; minimum bactericidal concentration [MBC], 0.03 to 1 μg/ml) except
Leuconostoc mesenteroides
, some gram-negative bacteria (8 of 14; MBC, >0.5 μg/ml), and some yeasts (3 of 9; MBC >3 μg/ml). Slight hemolytic activity (4.2% at 100 μg/ml) against human erythrocytes was observed only under low-ionic-strength conditions. Less than 1 min of contact was enough to kill
Staphylococcus aureus
ATCC 6538P. The bactericidal activity against
S. aureus
was inhibited by salts.
Prediction of Quinolone Activity against
Mycobacterium avium
by Molecular Topology and Virtual Computational Screening
Authors: Gozalbes Rafael , Brun-Pascaud Monique , García-Domenech Ramon , Gálvez Jorge , Girard Pierre-Marie , Doucet Jean-Pierre , Derouin Francis 
Published: July 2002

ABSTRACT

We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against
Mycobacterium avium-M. intracellulare
complex in order to develop a model capable of predicting the activity of new quinolones against the
M. avium-M. intracellulare
complex in vitro. Topological indices were used as structural descriptors and were related to anti-
M. avium-M. intracellulare
complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 24 quinolones, including recently developed fluoroquinolones, whose MICs were subsequently determined in vitro by using the Alamar blue microplate assay; the biological results confirmed the model's predictions. The MICs of these 24 quinolones were then treated by multilinear regression (MLR) to establish a model capable of classifying them according to their in vitro activities. Using this model, a good correlation between measured and predicted MICs was found (
r
2
= 0.88;
r
2
cv
[cross-validation correlation] = 0.82). Moxifloxacin, sparfloxacin, and gatifloxacin were the most potent against the
M. avium- M. intracellulare
complex, with MICs of 0.2, 0.4, and 0.9 μg/ml, respectively. Finally, virtual modifications of these three drugs were evaluated in LDA and MLR models in order to determine the importance of different substituents in their activity. We conclude that the combination of molecular-topology methods, LDA, and MLR provides an excellent tool for the design of new quinolone structures with enhanced activity.
Indinavir Pharmacokinetics and Parmacodynamics in Children with Human Immunodeficiency Virus Infection
Authors: Gatti Giorgio , Vigano' Alessandra , Sala Natascia , Vella Stefano , Bassetti Matteo , Bassetti Dante , Principi Nicola 
Published: July 2002

ABSTRACT

The indinavir dosage regimen currently used for human immunodeficiency virus (HIV)-infected children is not based on pharmacokinetic data obtained in the target patient population. The purpose of our study was to characterize indinavir pharmacokinetics and pharmacodynamics in HIV-infected children. Eleven children (age range, 9.0 to 13.6 years; weight range, 21.7 to 56.0 kg) receiving indinavir (500 mg/m
2
every 8 h) in combination with lamivudine and stavudine were studied. The correlation of indinavir pharmacokinetic parameters and demographic parameters was evaluated. Also, the pharmacodynamic relationship between parameters of indinavir exposure and parameters of renal toxicity and immunologic recovery was studied. The area under the indinavir concentration-time curve (AUC) and patient body surface area (BSA) showed a significant negative correlation (
r
= 0.73;
P
= 0.012). Patients with smaller BSA had excessive indinavir AUC compared to adults. On the other hand, the median minimum drug concentration in plasma (
C
min
) was lower than that reported for adults. The maximum indinavir concentration in serum was higher in patients with renal toxicity (5 out of 11 children), but the difference was not statistically significant (15.3 ± 8.2 versus 9.8 ± 4.4 mg/liter;
P
= 0.19). There was a trend toward higher immunologic efficacy in patients with greater indinavir exposure: the time-averaged AUC of the percentage of CD4
+
lymphocytes over the baseline value for patients with indinavir
C
min
> 95% inhibitory concentration (IC
95
) was higher than in patients with
C
min
< IC
95
(
P
= 0.068). Our study suggests that a dose reduction may be appropriate for children with small BSA and that a 6-h dosage regimen may be indicated for a substantial percentage of patients. Due to the low number of patients enrolled in this study, our results should be confirmed by a larger study.
Antimicrobial Activities of Mefloquine and a Series of Related Compounds
Authors: Kunin C. M. , Ellis W. Y. 
Published: July 2002

ABSTRACT

Mefloquine was found to have bactericidal activity against methicillin- and fluoroquinolone-susceptible and -resistant strains of
Staphylococcus aureus
and
Staphylococcus epidermidis
and gentamicin- and vancomycin-resistant strains of
Enterococcus faecalis
and
Enterococcus faecium
. The MICs were 16 μg/ml, and the minimal bactericidal concentrations (MBCs) were 16 to 32 μg/ml. These concentrations cannot be achieved in serum. Mefloquine was active at a more achievable concentration against penicillin-susceptible and -resistant
Streptococcus pneumoniae
, with MICs of 0.2 to 1.5 μg/ml. Mefloquine was not active against gram-negative bacteria and yeasts. In an attempt to find more active derivatives, 400 mefloquine-related compounds were selected from the chemical inventory of The Walter Reed Army Institute of Research. We identified a series of compounds containing a piperidine methanol group attached to pyridine, quinoline, and benzylquinoline ring systems. These had activities similar to that of mefloquine against
S. pneumoniae
but were far more active against other gram-positive bacteria (MICs for staphylococci, 0.8 to 6.3 μg/ml). They had activities similar to that of amphotericin B against
Candida
spp. and
Cryptococcus neoformans
. Combinations of the compounds with gentamicin and vancomycin were additive against staphylococci and pneumococci. The MIC and MBC of gentamicin were decreased by four- to eightfold when this drug was combined with limiting dilutions of the compounds. There was no antagonism with other antimicrobial drugs. The compounds were rapidly bactericidal. They appear to act by disrupting cell membranes. Combinations of the compounds with aminoglycoside antibiotics may have potential for therapeutic use.
Identification and Expression of Genes Involved in Biosynthesis of
l
-Oleandrose and Its Intermediate
l
-Olivose in the Oleandomycin Producer
Streptomyces antibioticus
Authors: Aguirrezabalaga Ignacio , Olano Carlos , Allende Nerea , Rodriguez Leticia , Braña Alfredo F. , Méndez Carmen , Salas José A. 
Published: July 2002

ABSTRACT

A 9.8-kb DNA region from the oleandomycin gene cluster in
Streptomyces antibioticus
was cloned. Sequence analysis revealed the presence of 8 open reading frames encoding different enzyme activities involved in the biosynthesis of one of the two 2,6-deoxysugars attached to the oleandomycin aglycone:
l
-oleandrose (the
oleW
,
oleV
,
oleL
, and
oleU
genes) and
d
-desosamine (the
oleNI
and
oleT
genes), or of both (the
oleS
and
oleE
genes). A
Streptomyces albus
strain harboring the
oleG2
glycosyltransferase gene integrated into the chromosome was constructed. This strain was transformed with two different plasmid constructs (pOLV and pOLE) containing a set of genes proposed to be required for the biosynthesis of dTDP-
l
-olivose and dTDP-
l
-oleandrose, respectively. Incubation of these recombinant strains with the erythromycin aglycon (erythronolide B) gave rise to two new glycosylated compounds, identified as
l
-3-
O
-olivosyl- and
l
-3-
O
-oleandrosyl-erythronolide B, indicating that pOLV and pOLE encode all enzyme activities required for the biosynthesis of these two 2,6-dideoxysugars. A pathway is proposed for the biosynthesis of these two deoxysugars in
S. antibioticus
.
Comparative Killing Rates of Fluoroquinolones and Cell Wall-Active Agents
Authors: Fung-Tomc Joan C. , Gradelski Elizabeth , Valera Lourdes , Kolek Benjamin , Bonner Daniel P. 
Published: July 2002

ABSTRACT

Killing rates of fluoroquinolones, β-lactams, and vancomycin were compared against
Enterobacteriaceae
,
Staphylococcus aureus
, pneumococci, streptococci, and
Enterococcus faecalis
. The times required for fluoroquinolones to decrease viability by 3 log
10
were 1.5 h for
Enterobacteriaceae
, 4 to 6 h for staphylococci, and ≥6 h for streptococci and enterococci. Thus, the rate of killing by fluoroquinolones is organism group dependent; overall, they killed more rapidly than β-lactams and vancomycin.
In Vitro Activity of Telithromycin (HMR3647), a New Ketolide, against Clinical Isolates of
Mycoplasma pneumoniae
in Japan
Authors: Yamaguchi Toshiyuki , Hirakata Yoichi , Izumikawa Koichi , Miyazaki Yoshitsugu , Maesaki Shigefumi , Tomono Kazunori , Yamada Yasuaki , Kamihira Shimeru , Kohno Shigeru 
Published: July 2002

ABSTRACT

The in vitro activity of telithromycin (HMR3647), a new ketolide, against
Mycoplasma pneumoniae
was determined by the broth microdilution test using 41 clinical isolates obtained in Japan, as compared with those of five macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin), minocycline, and levofloxacin. Telithromycin was less potent than azithromycin, but it was more active than four other macrolides, minocycline, and levofloxacin; its MICs at which 50 and 90% of the isolates tested were inhibited were both 0.00097 μg/ml, justifying clinical studies to determine its efficacy for treatment of
M. pneumoniae
.
Evidence for the Existence of a Multidrug Efflux Transporter Distinct from NorA in
Staphylococcus aureus
Authors: Kaatz Glenn W. , Seo Susan M. , O'Brien Louise , Wahiduzzaman Mohammad , Foster Timothy J. 
Published: July 2002

ABSTRACT

A
Staphylococcus aureus norA
disruption mutant was created by allelic replacement. Exposure of this mutant to norfloxacin produced SA K1748, a derivative with raised fluoroquinolone MICs, found to be the result of a
grlA
mutation, and raised organic cation MICs. Ethidium and enoxacin uptake was identical in SA K1748 and its parent, but pre-exposure of SA K1748 to organic cations caused a reduction in ethidium uptake as a result of increased efflux. Altered ethidium uptake and efflux, as well as increased MICs of other organic cations, suggest that SA K1748 possesses a non-NorA multidrug efflux transporter that is inducible by its substrates.
Quinolone Resistance in Enterotoxigenic
Escherichia coli
Causing Diarrhea in Travelers to India in Comparison with Other Geographical Areas
Authors: Vila Jordi , Vargas Martha , Ruiz Joaquim , Corachan Manuel , Jimenez de Anta M. Teresa , Gascon Joaquim 
Published: July 2002

ABSTRACT

Enterotoxigenic
Escherichia coli
isolates were identified as a cause of traveler's diarrhea in 82 of 520 (16%) patients and tested for resistance to seven antimicrobial agents. Thirty patients (36%) needed antimicrobial therapy: 17 (56%) for persistence of symptoms and 13 (44%) for severity of symptoms. Ampicillin, tetracycline, and trimethoprim-sulfamethoxazole resistance was high. Chloramphenicol showed moderate activity, and amoxicillin plus clavulanic acid, nalidixic acid, and ciprofloxacin showed very good activity. Five nalidixic acid-resistant strains were isolated, four from patients visiting India.
Failure of Azithromycin in Treatment of Brill-Zinsser Disease
Authors: Turčinov Drago , Kuzman Ilija , Herendić Boris 
Published: July 2002

ABSTRACT

Two patients suffering from Brill-Zinsser disease were treated with azithromycin, which did not prove effective.
Rickettsia prowazekii
, the agent causing Brill-Zinsser disease, cannot be treated with azithromycin. Both patients had epidemiological features consistent with and a clinical course typical of the disease. The diagnosis of Brill-Zinsser disease was serologically confirmed.
Genetic Localization and Molecular Characterization of the
nonS
Gene Required for Macrotetrolide Biosynthesis in
Streptomyces griseus
DSM40695
Authors: Smith Wyatt C. , Xiang Longkuan , Shen Ben 
Published: July 2002

ABSTRACT

The macrotetrolides are a family of cyclic polyethers derived from tetramerization, in a stereospecific fashion, of the enantiomeric nonactic acid (NA) and its homologs. Isotope labeling experiments established that NA is of polyketide origin, and biochemical investigations demonstrated that 2-methyl-6,8-dihydroxynon-2
E
-enoic acid can be converted into NA by a cell-free preparation from
Streptomyces lividans
that expresses
nonS
. These results lead to the hypothesis that macrotetrolide biosynthesis involves a pair of enantiospecific polyketide pathways. In this work, a 55-kb contiguous DNA region was cloned from
Streptomyces griseus
DSM40695, a 6.3-kb fragment of which was sequenced to reveal five open reading frames, including the previously reported
nonR
and
nonS
genes. Inactivation of
nonS
in vivo completely abolished macrotetrolide production. Complementation of the
nonS
mutant by the expression of
nonS
in
trans
fully restored its macrotetrolide production ability, with a distribution of individual macrotetrolides similar to that for the wild-type producer. In contrast, fermentation of the
nonS
mutant in the presence of exogenous (±)-NA resulted in the production of nonactin, monactin, and dinactin but not in the production of trinactin and tetranactin. These results prove the direct involvement of
nonS
in macrotetrolide biosynthesis. The difference in macrotetrolide production between in vivo complementation of the
nonS
mutant by the plasmid-borne
nonS
gene and fermentation of the
nonS
mutant in the presence of exogenously added (±)-NA suggests that NonS catalyzes the formation of (−)-NA and its homologs, supporting the existence of a pair of enantiospecific polyketide pathways for macrotetrolide biosynthesis in
S. griseus
. The latter should provide a model that can be used to study the mechanism by which polyketide synthase controls stereochemistry during polyketide biosynthesis.
In Vitro Antimicrobial Activities of Novel Anilinouracils Which Selectively Inhibit DNA Polymerase III of Gram-Positive Bacteria
Authors: Daly Jennifer S. , Giehl Theodore J. , Brown Neal C. , Zhi Chengxin , Wright George E. , Ellison Richard T. 
Published: July 2002

ABSTRACT

The 6-anilinouracils are novel dGTP analogs that selectively inhibit the replication-specific DNA polymerase III of gram-positive eubacteria. Two specific derivatives, IMAU (6-[3′-iodo-4′-methylanilino]uracil) and EMAU (6-[3′-ethyl-4′-methylanilino]uracil), were substituted with either a hydroxybutyl (HB) or a methoxybutyl (MB) group at their N3 positions to produce four agents: HB-EMAU, MB-EMAU, HB-IMAU, and MB-IMAU. These four new agents inhibited
Staphylococcus aureus
, coagulase-negative staphylococci,
Enterococcus faecalis
, and
Enterococcus faecium
. Time-kill assays and broth dilution testing confirmed bactericidal activity. These anilinouracil derivatives represent a novel class of antimicrobials with promising activities against gram-positive bacteria that are resistant to currently available agents, validating replication-specific DNA polymerase III as a new target for antimicrobial development.
A Spectrum of Changes Occurs in Peptidoglycan Composition of Glycopeptide-Intermediate Clinical
Staphylococcus aureus
Isolates
Authors: Boyle-Vavra Susan , Labischinski Harald , Ebert Christine C. , Ehlert Kerstin , Daum Robert S. 
Published: July 2002

ABSTRACT

The mechanism of glycopeptide resistance in
Staphylococcus aureus
is not known with certainty. Because the target of vancomycin is the
d
-Ala–
d
-Ala terminus of the stem peptide of the peptidoglycan precursor, by subjecting muropeptides to reversed-phase high-performance liquid chromatography, we investigated peptidoglycan obtained from glycopeptide-intermediate
S. aureus
(GISA) isolates for changes in composition and evaluated whether any peptidoglycan structural change was a consistent feature of clinical GISA isolates. GISA isolates Mu50 and Mu3 from Japan had the large glutamate-containing monomeric peak demonstrated previously, although strain H1, a vancomycin-susceptible MRSA isolate from Japan that was clonally related to Mu3 and Mu50, and a
femC
mutant that we studied, did also. For the U.S. GISA isolates, strain NJ had a large monomeric peak with a retention time identical to that described for the glutamate-containing monomer in strains H1, Mu3, and Mu50. However, a much smaller corresponding peak was seen in GISA MI, and this peak was absent from both GISA PC and a recent GISA isolate obtained from an adult patient in Illinois (strain IL). These data suggest that a uniform alteration in peptidoglycan composition cannot be discerned among the GISA isolates and indicate that a single genetic or biochemical change is unlikely to account for the glycopeptide resistance phenotype in the clinical GISA isolates observed to date. Furthermore, a large monomeric glutamate-containing peak is not sufficient to confer the resistance phenotype.
In Vitro Activities of Posaconazole (Sch 56592) Compared with Those of Itraconazole and Fluconazole against 3,685 Clinical Isolates of
Candida
spp. and
Cryptococcus neoformans
Authors: Pfaller M. A. , Messer S. A. , Hollis R. J. , Jones R. N. 
Published: July 2002

ABSTRACT

Posaconazole is a new investigational triazole with broad-spectrum antifungal activity. The in vitro activities of posaconazole were compared with those of itraconazole and fluconazole against 3,685 isolates of
Candida
spp. (3,312 isolates) and
C. neoformans
(373 isolates) obtained from over 70 different medical centers worldwide. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the National Committee for Clinical Laboratory Standards method using RPMI 1640 as the test medium. Posaconazole was very active against all
Candida
spp. (MIC at which 90% of the isolates were inhibited [MIC
90
], 0.5 μg/ml; 97% of MICs were ≤1 μg/ml) and
C. neoformans
(MIC
90
, 0.5 μg/ml; 100% of MICs were ≤1 μg/ml).
Candida albicans
was the most susceptible species of
Candida
(MIC
90
, 0.06 μg/ml), and
Candida glabrata
was the least susceptible (MIC
90
, 4 μg/ml). Posaconazole was more active than itraconazole and fluconazole against all
Candida
spp. and
C. neoformans
. These results provide further evidence for the spectrum and potency of posaconazole against a large and geographically diverse collection of clinically important fungal pathogens.
Two New Point Mutations at A2062 Associated with Resistance to 16-Membered Macrolide Antibiotics in Mutant Strains of
Mycoplasma hominis
Authors: Furneri Pio Maria , Rappazzo Giancarlo , Musumarra Maria Pia , Di Pietro Patrizia , Catania Lucrezia S. , Roccasalva Lucia Silvana 
Published: July 2002

ABSTRACT

We describe two mutants of
Mycoplasma hominis
PG-21 which show resistance to 16-membered macrolides but susceptibility to lincosamides, obtained by in vitro exposure to increasing doses of josamycin. The 23S rRNA gene showed that each had a mutation (A2062G and A2062T) corresponding to nucleotide 2062 in
Escherichia coli
, which was associated with the acquired phenotype.
Two-Year Surveillance of Antibiotic Resistance in
Streptococcus pneumoniae
in Four African Cities
Authors: Benbachir Mohamed , Benredjeb Saida , Boye Cheick Saadbouh , Dosso Mireille , Belabbes Houria , Kamoun Aouatef , Kaire Omar , Elmdaghri Naima 
Published: July 2002

ABSTRACT

Worldwide spread of antibiotic resistance in
Streptococcus pneumoniae
is a major problem. However, data from West and North African countries are scarce. To study the level of resistance and compare the situations in different cities, a prospective study was conducted in Abidjan (Ivory Coast), Casablanca (Morocco), Dakar (Senegal), and Tunis (Tunisia), from 1996 to 1997. The resistances to eight antibiotics of 375 isolates were studied by
E
test, and the results were interpreted using the breakpoints recommended by the National Committee for Clinical Laboratory Standards. Overall, 30.4% of the isolates were nonsusceptible to penicillin G (25.6% were intermediate and 4.8% were resistant). Amoxicillin (96.3% were susceptible) and parenteral third-generation cephalosporins (92.7%) were highly active. Resistance to chloramphenicol was detected in 8.6% of the isolates. High levels of resistance were noted for erythromycin (28%), tetracycline (38.3%), and cotrimoxazole (36.4%). Resistance to rifampin was rare (2.1%). There were significant differences in resistance rates between individual countries. Multiple resistance was more frequent in penicillin-nonsusceptible isolates than in penicillin-susceptible isolates. Recommendations for treatment could be generated from these results in each participating country.
Penicillin Pharmacodynamics in Four Experimental Pneumococcal Infection Models
Authors: Erlendsdottir Helga , Knudsen Jenny Dahl , Odenholt Inga , Cars Otto , Espersen Frank , Frimodt-Møller Niels , Fuursted Kurt , Kristinsson Karl G. , Gudmundsson Sigurdur 
Published: July 2002

ABSTRACT

Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of
Streptococcus pneumoniae
type 6B were used, one for which the penicillin MIC was 0.016 μg/ml and the other for which the penicillin MIC was 1.0 μg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (
C
max
s) and times that the concentrations were greater than the MIC (
T
>MIC
s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the
T
>MIC
and to a lesser extent on the
C
max
/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (∼6 log
10
CFU/ml), followed by the thigh (∼3 log
10
CFU/thigh), and being the lowest in the lung (∼1 log
10
CFU/lung). In the rabbit model the maximal effect was ∼6 log
10
CFU/ml after 24 h. In the mouse models bactericidal activity became marked when
T
>MIC
was ≥65% of the experimental time and
C
max
was ≥15 times the MIC, and in the rabbit model bactericidal activity became marked when
T
>MIC
was ≥35%,
C
max
was ≥5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the
C
max
/MIC ratio and
T
>MIC
, the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.