bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Responses to Different Antimalarial Drugs in Vivax Malaria
Authors: Pukrittayakamee Sasithon , Chantra Arun , Simpson Julie A. , Vanijanonta Sirivan , Clemens Ralf , Looareesuwan Sornchai , White Nicholas J. 
Published: July 2002

ABSTRACT

The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients with
Plasmodium vivax
malaria. This parasite does not cause marked sequestration, so parasite clearance can be used as a direct measure of antimalarial activity. The activities of these drugs in descending order were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, and pyrimethamine-sulfadoxine (PS). Therapeutic responses to PS were poor; parasitemias did not clear in 5 of the 12 PS-treated patients, whereas all the other patients made an initial recovery. Of 166 patients monitored for ≥28 days, 35% had reappearance of vivax malaria 11 to 65 days later and 7% developed falciparum malaria 5 to 21 days after the start of treatment. There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine, in which all vivax malaria reappearances developed >28 days after treatment, suggesting suppression of the first relapse by these slowly eliminated drugs. There was no evidence of chloroquine resistance. The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action.
Antipneumococcal Activity of ABT-773 Compared to Those of 10 Other Agents
Authors: Davies Todd A. , Ednie Lois M. , Hoellman Dianne M. , Pankuch Glenn A. , Jacobs Michael R. , Appelbaum Peter C. 
Published: July 2002

ABSTRACT

MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78
ermB
- and 44
mefE
-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC
50
s) and MIC
90
s were 0.016 to 0.03 and 0.125 μg/ml, respectively. Clindamycin was active only against macrolide-resistant strains containing
mefE
(MIC
50
, 0.06 μg/ml; MIC
90
, 0.125 μg/ml). Activities of pristinamycin (MIC
90
, 0.5 μg/ml) and vancomycin (MIC
90
, 0.25 μg/ml) were unaffected by macrolide or penicillin resistance, while β-lactam MICs rose with those of penicillin G. Against 19 strains with L4 ribosomal protein mutations and two strains with mutations in domain V of 23S rRNA, ABT-773 MICs were 0.03 to 0.25 μg/ml, while macrolide and azalide MICs were all ≥16.0 μg/ml. ABT-773 was bactericidal at twice the MIC after 24 h for 8 of 12 strains (including three strains with erythromycin MICs greater than or equal to 64.0 μg/ml). Kill kinetics of erythromycin, azithromycin, clarithromycin, and roxithromycin against macrolide-susceptible strains were slower than those of ABT-773. ABT-773 had longer PAEs than macrolides, azithromycin, clindamycin, or β-lactams, including against
ermB
-containing strains. ABT-773, therefore, shows promising in vitro activity against macrolide-susceptible as well as -resistant pneumococci.
Prevalence and Characteristics of Multinucleoside-Resistant Human Immunodeficiency Virus Type 1 among European Patients Receiving Combinations of Nucleoside Analogues
Authors: Van Vaerenbergh Kristien , Van Laethem Kristel , Albert Jan , Boucher Charles A. B. , Clotet Bonaventura , Floridia Marco , Gerstoft Jan , Hejdeman Bo , Nielsen Claus , Pannecouque Christophe , Perrin Luc , Pirillo Maria F. , Ruiz Lidia , Schmit Jean-Claude , Schneider François , Schoolmeester Anne , Schuurman Rob , Stellbrink Hans J. , Stuyver Lieven , Van Lunzen Jan , Van Remoortel Barbara , Van Wijngaerden Eric , Vella Stefano , Witvrouw Myriam , Yerly Sabine , De Clercq Erik , Desmyter Jan , Vandamme Anne-Mieke 
Published: July 2002

ABSTRACT

The prevalence and the genotypic and phenotypic characteristics of multinucleoside-resistant (MNR) human immunodeficiency virus type 1 (HIV-1) variants in Europe were investigated in a multicenter study that involved centers in nine European countries. Study samples (
n
= 363) collected between 1991 and 1997 from patients exposed to two or more nucleoside analogue reverse transcriptase inhibitors (NRTIs) and 274 control samples from patients exposed to no or one NRTI were screened for two marker mutations of multinucleoside resistance (the Q151M mutation and a mutation with a 2-amino-acid insertion at codon 69, T69S-XX). Q151M was identified in six of the study samples (1.6%), and T69S-XX was identified in two of the study samples (0.5%; both of them T69S-SS), but both patterns were absent among control samples. Non-NRTI (NNRTI)-related changes were observed in viral strains from two patients, which displayed the Q151M resistance pattern, although the patients were NNRTI naive. The patients whose isolates displayed multinucleoside resistance had received treatment with zidovudine and either didanosine, zalcitabine, or stavudine. Both resistance patterns conferred broad cross-resistance to NRTIs in vitro and a poor response to treatment in vivo. MNR HIV-1 is found only among multinucleoside-experienced patients. Its prevalence is low in Europe, but it should be closely monitored since it seriously limits treatment options.
Therapeutic Efficacy of Liposomal Rifabutin in a
Mycobacterium avium
Model of Infection
Authors: Gaspar Maria Manuela , Neves Susana , Portaels Françoise , Pedrosa Jorge , Silva Manuel T. , Cruz Maria Eugénia M. 
Published: July 2002

ABSTRACT

Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied. The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of infection with a virulent
Mycobacterium avium
strain (strain P1581) and was compared with that of free rifabutin. The influences of the size of the liposomal rifabutin formulation, the administered doses, and the treatment schedules on the evolution of infection were studied. Two types of treatment schedules were assayed: therapeutic and prophylactic. The therapeutic treatment started 2 weeks after infection, while the prophylactic treatment began 1 day before the experimental infection with mycobacteria. Incorporation of rifabutin in liposomes resulted in a significant enhancement of activity against
M. avium
infection compared to that of rifabutin in the free form in both schedules. These results demonstrate that liposomal formulations of antibiotics such as rifabutin may be effective for the treatment or prophylaxis of infectious diseases.
Bactericidal Activity of Micromolar
N
-Chlorotaurine: Evidence for Its Antimicrobial Function in the Human Defense System
Authors: Nagl Markus , Hess Michael W. , Pfaller Kristian , Hengster Paul , Gottardi Waldemar 
Published: July 2002

ABSTRACT

N
-Chlorotaurine, the main representative of long-lived oxidants found in the supernatant of stimulated granulocytes, has been investigated systematically with regard to its antibacterial activity at different physiological concentrations for the first time.
N
-Chlorotaurine (12.5 to 50 μM) demonstrated a bactericidal effect i.e., a 2 to 4 log
10
reduction in viable counts, after incubation at 37°C for 6 to 9 h at pH 7.0, which effect was significantly enhanced in an acidic milieu (at pH 5.0), with a 3 to 4 log
10
reduction after 2 to 3 h. Moreover, bacteria were attenuated after being incubated in
N
-chlorotaurine for a sublethal time, as demonstrated with the mouse peritonitis model. The supernatant of stimulated granulocytes exhibited similar activity. Transmission electron microscopy revealed changes in the bacterial cell membrane and cytoplasmic disintegration with both reacting systems, even in the case of a mere attenuation. The results of this study suggest a significant bactericidal function of
N
-chlorotaurine and other chloramines during inflammation.
Comparative In Vitro Activities of ABT-773 against Aerobic and Anaerobic Pathogens Isolated from Skin and Soft-Tissue Animal and Human Bite Wound Infections
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi , Tyrrell Kerin 
Published: July 2002

ABSTRACT

We studied the comparative in vitro activities of ABT-773, a new ketolide, against 268 aerobic and 148 anaerobic recent isolates from clinical bites using an agar dilution method and inocula of 10
4
CFU/spot for aerobes and 10
5
CFU for anaerobes. The following are the MIC ranges and MICs at which 90% of isolates are inhibited (MIC
90
s) of ABT-773 for various isolates, respectively:
Pasteurella multocida
and
Pasteurella septica
, 0.125 to 2 and 1 μg/ml; other
Pasteurella
species, 0.125 to 1 and 0.5 μg/ml;
Corynebacterium
spp., 0.015 to 0.06 and 0.015 μg/ml;
Staphylococcus aureus
, 0.03 to 0.06 and 0.06 μg/ml; coagulase-negative staphylococci, 0.015 to >32 and 32 μg/ml; streptococci, 0.015 to 0.03 and 0.03 μg/ml;
Eikenella corrodens
, 0.25 to 1 and 1 μg/ml; and
Bergeyella zoohelcum
, 0.03 to 0.25 and 0.06 μg/ml. For anaerobes the MIC ranges and MIC
90
s of ABT-773 were as follows, respectively:
Prevotella heparinolytica
, 0.06 to 0.125 and 0.125 μg/ml;
Prevotella
spp., 0.015 to 0.125 and 0.06 μg/ml;
Porphyromonas
spp., 0.015 to 0.03 and 0.015 μg/ml;
Fusobacterium nucleatum
, 0.5 to 8 and 8 μg/ml; other
Fusobacterium
spp., 0.015 to 8 and 0.5 μg/ml;
Bacteroides tectum
, 0.015 to 0.5 and 0.06 μg/ml; and
Peptostreptococcus
spp., 0.015 to 0.25 and 0.03 μg/ml. ABT-773 was more active than all macrolides tested against
S. aureus
,
E. corrodens
, and anaerobes, but all compounds were poorly active against
F. nucleatum
. The activity of ABT-773 was within 1 dilution of that of azithromycin against
Pasteurella
spp., and ABT-773 was four- to eightfold more active than clarithromycin against
Pasteurella
spp. ABT-773 may offer a therapeutic alternative for bite wound infections.
Pharmacokinetics of Oral Acyclovir in Neonates and in Infants: a Population Analysis
Authors: Tod M. , Lokiec F. , Bidault R. , De Bony F. , Petitjean O. , Aujard Y. ,   the Acyclovir Pediatric French Group
Published: July 2002

ABSTRACT
Acyclovir is approved for the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in children by the intravenous and oral routes. However, its use by the oral route in children younger than 2 years of age is limited due to a lack of pharmacokinetic data. The objectives of the present study were to determine the typical pharmacokinetics of an oral suspension of acyclovir given to children younger than 2 years of age and the interindividual variabilities in the values of the pharmacokinetic parameters in order to support the proposed dosing regimen (24 mg/kg of body weight three times a day for patients younger than 1 month of age or four times a day otherwise). Children younger than age 2 years with HSV or VZV infections were enrolled in a multicenter study. Children were treated for at least 5 days with an acyclovir oral suspension. Plasma samples were obtained at steady state, before acyclovir administration, and at 2, 3, 5, and 8 h after acyclovir administration. Acyclovir concentrations were measured by radioimmunoassay. The data were analyzed by a population approach. Data for 79 children were considered in the pharmacokinetic study (212 samples, 1 to 5 samples per patient). Acyclovir clearance was related to the estimated glomerular filtration rate, body surface area, and serum creatinine level. The volume of distribution was related to body weight. The elimination half-life decreased sharply during the first month after birth, from 10 to 15 h to 2.5 h. Bioavailability was 0.12. The interindividual variability was less pronounced when the parameters were normalized with respect to body weight. Hence, dosage adjustment by body weight is recommended for this population. Simulations showed that the length of time that acyclovir remains above the 50% inhibitory concentration during a 24-h period was more than 12 h for HSV but not for VZV. The proposed dosing regimen seems adequate for the treatment of HSV infections, while for the treatment of VZV infections, a twofold increase in the dose seems necessary for children older than age 3 months.
Pharmacodynamics of Telithromycin In Vitro against Respiratory Tract Pathogens
Authors: Odenholt Inga , Löwdin Elisabeth , Cars Otto 
Published: July 2002

ABSTRACT

Telithromycin (HMR 3647) is a new ketolide that belongs to a new class of semisynthetic 14-membered-ring macrolides which have expanded activity against multidrug-resistant gram-positive bacteria. The aim of the present study was to investigate different basic pharmacodynamic properties of this new compound. The following studies of telithromycin were performed: (i) studies of the rate and extent of killing of respiratory tract pathogens with different susceptibilities to erythromycin and penicillin exposed to a fixed concentration that corresponds to a dose of 800 mg in humans, (ii) studies of the rate and extent of killing of telithromycin at five different concentrations, (iii) studies of the rate and extent of killing of the same pathogens at three different inocula, (iv) studies of the postantibiotic effect and the postantibiotic sub-MIC effect of telithromycin, and (v) determination of the rate and extent of killing of telithromycin in an in vitro kinetic model. In conclusion, telithromycin exerted an extremely fast killing of all strains of
Streptococcus pneumoniae
both with static concentrations and in the in vitro kinetic model. A slower killing of the strains of
Streptococcus pyogenes
was noted, with regrowth in the kinetic model of a macrolide-lincosamide-streptogramin B-inducible strain. The strains of
Haemophilus influenzae
were not killed at all at a concentration of 0.6 mg/liter due to high MICs. A time-dependent killing was seen for all strains. No inoculum effect was seen for the strains of
S. pneumoniae
, with a 99.9% reduction in the numbers of CFU for all inocula at both 8 h and 24 h. The killing of the strains of
S. pyogenes
was reduced by 1 log
10
CFU at 8 h and 2 to 3 log
10
CFU at 24 h when the two lower inocula were used but not at all at 8 and 24 h when the highest inoculum was used. For both of the
H. influenzae
strains there was an inoculum effect, with 1 to 2 log
10
CFU less killing for the inoculum of 10
8
CFU/ml in comparison to that for the inoculum of 10
6
CFU/ml. Overall, telithromycin exhibited long postantibiotic effects and postantibiotic sub-MIC effects for all strains investigated.
Comparative In Vitro Activities of ABT-773 against 362 Clinical Isolates of Anaerobic Bacteria
Authors: Citron Diane M. , Appleman Maria D. 
Published: July 2002

ABSTRACT

The activity of ABT-773, a novel ketolide antibiotic, against clinical isolates of anaerobic bacteria was determined and compared to the activities of other antimicrobial agents. MICs at which 90% of isolates were inhibited (MIC
90
s) were ≤0.06 μg/ml for
Actinomyces
spp.,
Clostridium perfringens
,
Peptostreptococcus
spp.,
Propionibacterium
spp., and
Porphyromonas
spp. The MIC
50
s and MIC
90
s were ≤0.06 and >32 μg/ml, respectively, for
Eubacterium
spp.,
Lactobacillus
spp.,
Clostridium difficile
, and
Clostridium ramosum.
The MIC
90
for
Bilophila wadsworthia
,
Bacteroides ureolyticus,
and
Campylobacter gracilis
was 1 μg/ml, and that for
Prevotella bivia
and other
Prevotella
spp. was 0.5 μg/ml. The MIC
90
for
Fusobacterium nucleatum
was 8 μg/ml, and that for
Fusobacterium mortiferum
and
Fusobacterium varium
was >32 μg/ml
.
The MIC
90
s for the
Bacteroides fragilis
group were as follows: for
B. fragilis
, 8 μg/ml; for
Bacteroides thetaiotaomicron
,
Bacteroides ovatus
,
Bacteroides distasonis
, and
Bacteroides uniformis
, >32 μg/ml; and for
Bacteroides vulgatus
, 4 μg/ml. Telithromycin MICs for the
B. fragilis
group were usually 1 to 2 dilutions higher than ABT-773 MICs. For all strains, ABT-773 was more active than erythromycin by 4 or more dilutions, and for some strains this drug was more active than clindamycin.
Pharmacokinetic Profiles of Nevirapine and Indinavir in Various Fractions of Seminal Plasma
Authors: van Praag Rieneke M. E. , Repping Sjoerd , de Vries Jan W. A. , Lange Joep M. A. , Hoetelmans Richard M. W. , Prins Jan M. 
Published: July 2002

ABSTRACTLimited data are available on antiretroviral drug concentrations in seminal plasma during a dosing interval. Further, since human ejaculate is composed of fluids originating from the testes, the seminal vesicles, and the prostate, all having different physiological characteristics, drug concentrations in total seminal plasma do not necessarily reflect concentrations in the separate compartments. Five human immunodeficiency virus type 1-infected patients on nevirapine (NVP; 200 mg twice a day [b.i.d.]) and/or indinavir (IDV; 800 mg b.i.d. with ritonavir, 100 mg b.i.d.) regimens used a split ejaculate technique to separate seminal plasma in two fractions, representing fluids from the testes and prostate (first fraction) and fluids from the seminal vesicles (second fraction). Split-ejaculate samples were provided at 0, 2, 5, and 8 h after drug ingestion, on separate days after 3 days of sexual abstinence. NVP and IDV showed time-dependent concentrations in seminal plasma, with peak concentrations in both fractions at 2 and 2 to 5 h, respectively, after drug ingestion. The NVP concentrations were not significantly different between the first and second fractions of the ejaculate at all time points measured and were in the therapeutic range, except for the predose concentration in two patients. The median (range) predose IDV concentrations in the first and second fractions of the ejaculate were 448 (353 to 1,015) ng/ml and 527 (240 to 849) ng/ml, respectively (P= 0.7). In conclusion, NVP and IDV concentrations in seminal plasma are dependent on the time after drug ingestion. Furthermore, our data suggest that NVP and IDV achieve therapeutic concentrations in both the testes and prostate and the seminal vesicles throughout the dosing interval.
Therapeutic Efficacy of Liposome-Encapsulated Gentamicin in Rat
Klebsiella pneumoniae
Pneumonia in Relation to Impaired Host Defense and Low Bacterial Susceptibility to Gentamicin
Authors: Schiffelers Raymond M. , Storm Gert , ten Kate Marian T. , Bakker-Woudenberg Irma A. J. M. 
Published: July 2002

ABSTRACT

Long-circulating liposomes (LCL) may be used as targeted antimicrobial drug carriers as they localize at sites of infection. As a result, LCL-encapsulated gentamicin (LE-GEN) has demonstrated superior antibacterial activity over the free drug in a single-dose study of immunocompetent rats with
Klebsiella pneumoniae
pneumonia. In the present study, the therapeutic efficacy of LE-GEN was evaluated by monitoring rat survival and bacterial counts in blood and lung tissue in clinically relevant models, addressing the issue of impaired host defense and low bacterial antibiotic susceptibility. The results show that in immunocompetent rats infected with the high-GEN-susceptibility
K. pneumoniae
strain, a single dose of LE-GEN is clearly superior to an equivalent dose of free GEN. Yet complete survival can also be obtained with multiple doses of free GEN. In leukopenic rats infected with the high-GEN-susceptible
K. pneumoniae
strain, free GEN at the maximum tolerated dose (MTD) was needed to obtain survival. However, with the addition of a single dose of LE-GEN to free-GEN treatment, complete survival can be obtained using a sevenfold-lower cumulative amount of GEN than with free-GEN treatment alone. In leukopenic rats infected with low-GEN-susceptible
K. pneumoniae
cells, free GEN at the MTD did not result in survival. The use of LE-GEN is needed for therapeutic success. Increasing LE-GEN bilayer fluidity resulted in an increased GEN release from the liposomes and hence improved rat survival, thus showing the importance of the liposome lipid composition for therapeutic efficacy. These results warrant further clinical studies of liposomal formulations of aminoglycosides in immunocompromised patients with severe infections.
Antimicrobial Properties and Mode of Action of the Pyrrothine Holomycin
Authors: Oliva Brunello , O'Neill Alexander , Wilson Jenny M. , O'Hanlon Peter J. , Chopra Ian 
Published: July 2002

ABSTRACT

Holomycin, a member of the pyrrothine class of antibiotics, displayed broad-spectrum antibacterial activity, inhibiting a variety of gram-positive and gram-negative bacteria, with the exception of
Enterobacter cloacae, Morganella morganii
, and
Pseudomonas aeruginosa
. The antibiotic lacked activity against the eukaryotic microorganisms
Saccharomyces cerevisiae
and
Candida kefyr
. Holomycin exhibited a bacteriostatic response against
Escherichia coli
that was associated with rapid inhibition of RNA synthesis in whole cells. Inhibition of RNA synthesis could have been a secondary consequence of inhibiting tRNA aminoacylation, thereby inducing the stringent response. However, the levels of inhibition of RNA synthesis by holomycin were similar in a stringent and relaxed pair of
E. coli
strains that were isogenic except for the deletion of the
relA
gene. This suggests that inhibition of RNA synthesis by holomycin could reflect direct inhibition of DNA-dependent RNA polymerase. Examination of the effects of holomycin on the kinetics of the appearance of β-galactosidase in induced
E. coli
cells was also consistent with inhibition of RNA polymerase at the level of RNA chain elongation. However, holomycin only weakly inhibited
E. coli
RNA polymerase in assays using synthetic poly(dA-dT) and plasmid templates. Furthermore, inhibition of RNA polymerase was observed only at holomycin concentrations in excess of those required to inhibit the growth of
E. coli
. It is possible that holomycin is a prodrug, requiring conversion in the cell to an active species that inhibits RNA polymerase.
In Vitro Activities of the New Ketolide HMR 3647 (Telithromycin) in Comparison with Those of Eight Other Antibiotics against Viridans Group Streptococci Isolated from Blood of Neutropenic Patients with Cancer
Authors: Alcaide Fernando , Benı́tez Miguel Angel , Carratalà Jordi , Gudiol Francesc , Liñares Josefina , Martı́n Rogelio 
Published: July 2002

ABSTRACT
The in vitro activities of the ketolide telithromycin and eight other antibiotics were tested against 77 strains of viridans group streptococci isolated from blood samples of neutropenic patients. Thirty-one (40.3%) of the strains were resistant to penicillin G, and 27 (35.1%) were resistant to erythromycin A. Telithromycin (MIC range of ≤0.03 to 1 μg/ml) was the most active antimicrobial tested. These data suggest that telithromycin could be useful for treatment of viridans group streptococcal bacteremia in neutropenic patients with cancer.