bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of a New Parenteral Oligosaccharide Antibiotic, SCH27899 (Ziracin), in Healthy Subjects
Authors: Kozawa Osamu , Uematsu Toshihiko , Matsuno Hiroyuki , Niwa Masayuki , Kohno Ken-Ichi , Kawato Asakazu , Takahashi Kazuyoshi , Nagashima Satoru , Kanamaru Mitsutaka 
Published: July 2002

ABSTRACT

The pharmacokinetic properties of an everninomicin antibiotic (SCH27899; Ziracin) were studied with healthy Japanese male volunteers by single (1, 3, 6, and 9 mg/kg of body weight) and multiple 60-min intravenous infusions (3, 6, and 9 mg/kg once daily for 10 consecutive days following a 2-day interval after the initial dose). At single doses the peak serum concentration and the area under the serum concentration-time curve linearly increased with the dose. While total body clearance (CL; 31.2 to 45.6 ml/kg/h) and percent cumulative urinary recovery as unchanged drug (4.9 to 7.1%) were rather constant irrespective of doses, the terminal half-life of γ phase (
t
1/2γ
; 14.2 to 19.6 h) were slightly prolonged at the higher two doses compared with the lower two doses. With repeated doses of SCH27899, a statistically significant decrease and increase were found in CL and
t
1/2γ
of about 36 and 21%, respectively, although these changes may be clinically irrelevant. The most commonly reported adverse events were local reactions such as erythema, pain, and palpable venous cord of mild to moderate degree around the injection site, which could be managed by changing the injection sites.
Efficacies of Gel Formulations Containing Foscarnet, Alone or Combined with Sodium Lauryl Sulfate, against Establishment and Reactivation of Latent Herpes Simplex Virus Type 1
Authors: Piret Jocelyne , Lamontagne Julie , Désormeaux André , Bergeron Michel G. 
Published: July 2002

ABSTRACT
The influence of sodium lauryl sulfate (SLS) on the efficacies of gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous lesions and on the establishment and reactivation of latent virus has been evaluated in a murine model of orofacial infection. Topical treatments were given twice daily for 3 days and were initiated at 6, 24, and 48 h after virus inoculation. The gel formulation that contained both 3% foscarnet and 5% SLS and that was administered within 48 h postinfection reduced the rate of development of herpetic skin lesions. This formulation also significantly decreased the viral content in skin tissues and in ipsilateral trigeminal ganglia when it was given within 24 and 6 h postinfection, respectively. A lower level of efficacy was observed for the gel formulation containing 3% foscarnet alone. Of prime interest, the gel formulation containing 5% SLS reduced significantly the mortality rate among mice in a zosteriform model of infection. Both formulations of foscarnet had no effect on the mean titers of reactivated virus in explant cultures of ipsilateral and contralateral trigeminal ganglia from latently infected mice. The use of a gel formulation containing combinations of foscarnet and SLS could represent an attractive approach for the treatment of herpetic mucocutaneous infections.
Specific Inhibition of Coxsackievirus B3 Translation and Replication by Phosphorothioate Antisense Oligodeoxynucleotides
Authors: Wang Aikun , Cheung Paul K. M. , Zhang Huifang , Carthy Christopher M. , Bohunek Lubos , Wilson Janet E. , McManus Bruce M. , Yang Decheng 
Published: July 2002

ABSTRACT
The 5′ and 3′ untranslated regions (UTRs) of coxsackievirus B3 (CVB3) RNA form highly ordered secondary structures that have been confirmed to play important regulatory roles in viral cap-independent internal translation initiation and RNA replication. We previously demonstrated that deletions in different regions of the 5′ UTR significantly reduced viral RNA translation and infectivity. Such observations suggested strongly that viral RNA translation and replication could be blocked if highly specific antisense oligodeoxynucleotides (AS-ODNs) were applied to target crucial sites within the 5′ and 3′ UTRs. In this study, seven phosphorothioate AS-ODNs were synthesized, and the antiviral activity was evaluated by Lipofectin transfection of HeLa cells with AS-ODNs followed by infection of CVB3. Analysis by Western blotting, reverse transcription-PCR, and viral plaque assay demonstrated that viral protein synthesis, genome replication, and infectivity of CVB3 were strongly inhibited by the AS-ODNs complementary to different regions of the 5′ and 3′ UTRs. The most effective sites are located at the proximate terminus of the 5′ UTR (AS-1), the proximate terminus of the 3′ UTR (AS-7), the core sequence of the internal ribosome entry site (AS-2), and the translation initiation codon region (AS-4). These AS-ODNs showed highly sequence-specific and dose-dependent inhibitory effects on both viral protein synthesis and RNA replication. It is noteworthy that the highest inhibitory activities were obtained with AS-1 and AS-7 targeting the termini of the 5′ and 3′ UTRs. The percent inhibition values of AS-1 and AS-7 for CVB3 protein VP1 synthesis and RNA replication were 70.6 and 79.6 for AS-1 and 73.7 and 79.7 for AS-7, respectively. These data suggest that CVB3 infectivity can be inhibited effectively by AS-ODNs.
In Vitro Activities of Six Quinolones and Mechanisms of Resistance in
Staphylococcus aureus
and Coagulase-Negative Staphylococci
Authors: Linde Hans-Jörg , Schmidt Mario , Fuchs Emmi , Reischl Udo , Niller Hans-Helmut , Lehn Norbert 
Published: July 2002

ABSTRACT

Of 94 clinical isolates of
Staphylococcus aureus
(
n
= 51) and coagulase-negative staphylococci (CNS) (
n
= 43), mutations in the quinolone resistance-determining region of topoisomerases GrlA, GrlB, GyrA, and GyrB together with MICs of six quinolones were analyzed. Amino acid substitutions at identical residues (GrlA residues 80 and 84; GyrA residues 84 and 88) were found in
S. aureus
and CNS. Active efflux, as suggested by blocking by reserpine, contributed substantially to the resistance phenotype in some strains. Among ciprofloxacin, clinafloxacin, levofloxacin, nalidixic acid, trovafloxacin, and sparfloxacin, a 0.5-μg/ml concentration of sparfloxacin discriminated best between strains with two or three mutations and those with no mutations.
Macrolide Resistance in
Streptococcus pneumoniae
in Hong Kong
Authors: Ip Margaret , Lyon Donald J. , Yung Raymond W. H. , Chan Colin , Cheng Augustine F. B. 
Published: July 2002

ABSTRACT

Erythromycin resistance rates among penicillin-susceptible
Streptococcus pneumoniae
were 38 and 92% among penicillin-intermediate and -resistant
S. pneumoniae
isolates from Hong Kong, respectively, and 27% (43 of 158) of the isolates showed the MLS
B
phenotype, and the majority carried the
ermB
gene; 73% (115 of 158) displayed the M phenotype, and all possessed the
mef
gene. The MLS
B
phenotype was predominant in penicillin-susceptible, macrolide-resistant isolates and in penicillin-nonsusceptible isolates of serotype 6B, whilst the M phenotype was predominant in penicillin-intermediate or -resistant isolates belonging to serotype 23F or 19F. Extensive spread of clones of drug-resistant pneumococci has led to the widespread presence of macrolide resistance in
S. pneumoniae
in Hong Kong.
Mechanism of Synergy between Epigallocatechin Gallate and β-Lactams against Methicillin-Resistant
Staphylococcus aureus
Authors: Zhao Wei-Hua , Hu Zhi-Qing , Okubo Sachie , Hara Yukihiko , Shimamura Tadakatsu 
Published: July 2002

ABSTRACT

Compared to MICs (more than 800 μg/ml) of (−)-epigallocatechin gallate (EGCg) against
Escherchia coli
, MICs of EGCg against methicillin-susceptible and methicillin-resistant
Staphylococcus aureus
(MSSA and MRSA) were 100 μg/ml or less. Furthermore, less than 25 μg EGCg per ml obviously reversed the high level resistance of MRSA to all types of tested β-lactams, including benzylpenicillin, oxacillin, methicillin, ampicillin, and cephalexin. EGCg also induced a supersusceptibility to β-lactams in MSSA which does not express
mecA
, encoding penicillin-binding protein 2′ (PBP2′). The fractional inhibitory concentration (FIC) indices of the tested β-lactams against 25 isolates of MRSA were from 0.126 to 0.625 in combination with 6.25, 12.5 or 25 μg of EGCg per ml. However, no synergism was observed between EGCg and ampicillin against
E. coli
. EGCg largely reduced the tolerance of MRSA and MSSA to high ionic strength and low osmotic pressure in their external atmosphere, indicating damage of the cell wall. Unlike dextran and lipopolysaccharide, peptidoglycan from
S. aureus
blocked both the antibacterial activity of EGCg and the synergism between EGCg and oxacillin, suggesting a direct binding of EGCg with peptidoglycan on the cell wall. EGCg showed a synergistic effect with
dl
-cycloserine (an inhibitor of cell wall synthesis unrelated to PBP2′) but additive or indifferent effect with inhibitors of protein and nuclear acid synthesis. EGCg did not suppress either PBP2′ mRNA expression or PBP2′ production, as confirmed by reverse transcription-PCR and a semiquantitative PBP2′ latex agglutination assay, indicating an irrelevance between the synergy and PBP2′ production. In summary, both EGCg and β-lactams directly or indirectly attack the same site, peptidoglycan on the cell wall. EGCg synergizes the activity of β-lactams against MRSA owing to interference with the integrity of the cell wall through direct binding to peptidoglycan.
Durability of Anti-Infective Effect of Long-Term Silicone Sheath Catheters Impregnated with Antimicrobial Agents
Authors: Tcholakian Robert K. , Raad Issam I. 
Published: July 2002

ABSTRACT
This study was performed to test the long-term antimicrobial efficacy of impregnated silicone catheters comprising an antimicrobial layer sandwiched between an external surface sheath and a luminal surface silicone sheath. The design of the catheter permits the introduction of various antimicrobials in addition to anticoagulants or antifibrins in the antimicrobial layer and allows their gradual release over a period of months after insertion. The in vitro data presented show that the catheter can provide antimicrobial activity for 90 days, after being replated for 15 7-day cycles of replating. When the catheters were immersed in human serum and incubated at 37°C, they demonstrated significant antimicrobial activity after more than 325 days of incubation. The significant long-term in vitro antimicrobial activity observed may imply effective in vivo activity for almost 1 year after insertion and could serve as a cost-effective alternative to surgically implantable silicone catheters.
Alterations in MurM, a Cell Wall Muropeptide Branching Enzyme, Increase High-Level Penicillin and Cephalosporin Resistance in
Streptococcus pneumoniae
Authors: Smith Anthony M. , Klugman Keith P. 
Published: July 2002

ABSTRACT

We report that alteration in MurM, an enzyme involved in the biosynthesis of branched-stem cell wall muropeptides, is required for maximal expression of penicillin and cefotaxime resistance in the pneumococcus. Hungarian isolate 3191 (penicillin MIC, 16 μg/ml; cefotaxime MIC, 4 μg/ml) was a source of donor DNA in transformation experiments. Penicillin-binding protein DNA was insufficient to transform recipient strain R6 to full resistance. Further transformation with altered
murM
DNA was required for full expression of donor penicillin and cefotaxime resistance.
Aminoglycoside Resistance with Homogeneous and Heterogeneous Populations of Antibiotic-Resistant Ribosomes
Authors: Recht Michael I. , Puglisi Joseph D. 
Published: July 2002

ABSTRACT

Aminoglycosides bind to rRNA in the small subunit of the bacterial ribosome. Mutations in the decoding region of 16S rRNA confer resistance to specific subsets of aminoglycoside antibiotics. The two major classes of 2-deoxystreptamine aminoglycosides are the 4,5- and the 4,6-disubstituted antibiotics. Antibiotics of the 4,5-disubstituted class include neomycin, paromomycin, and ribostamycin. Gentamicins and kanamycins belong to the 4,6-disubstituted class of aminoglycosides. Structural studies indicated the potential importance of position 1406 (
Escherichia coli
numbering) in the binding of ring III of the 4,6-disubstituted class of aminoglycosides to 16S rRNA. We have introduced a U1406-to-A mutation in a plasmid-encoded copy of
E. coli
16S rRNA which has been expressed either in a mixture with wild-type ribosomes or in a strain in which all rRNA is transcribed from the plasmid-encoded
rrn
operon. High-level resistance to many of the 4,6-disubstituted aminoglycosides is observed only when all the rRNA contains the U1406-to-A mutation. In contrast to the partial dominance of resistance observed with other mutations in the decoding region, there is a dominance of sensitivity with the 1406A mutation. Chemical footprinting experiments indicate that resistance arises from a reduced affinity of the antibiotic for the rRNA target. These results demonstrate that although position 1406 is an important determinant in the binding and action of the 4,6-disubstituted aminoglycosides, other rRNA mutations that perturb the binding of ring I of both classes of 2-deoxystreptamine aminoglycosides confer higher levels of resistance as well as a partial dominance of resistance.
Antipneumococcal Activity of BMS 284756 Compared to Those of Six Other Agents
Authors: Pankuch Glenn A. , Nagai Kensuke , Davies Todd A. , Jacobs Michael R. , Appelbaum Peter C. 
Published: July 2002

ABSTRACT
Antipneumococcal activity of BMS 284756 was compared to those of six agents by MIC and time-kill methodologies. BMS 284756 had the lowest MICs compared to those of ciprofloxacin, levofloxacin, and moxifloxacin against quinolone-susceptible (≤0.016 to 0.06 μg/ml) and quinolone-resistant (0.03 to 1 μg/ml) pneumococci. BMS 284756 was bactericidal against 11 of 12 strains at two times the MIC after 24 h.
Efficacy of Ceftriaxone and Gentamicin Given Once a Day by Using Human-Like Pharmacokinetics in Treatment of Experimental Staphylococcal Endocarditis
Authors: Gavaldà Joan , López Pedro , Martín Teresa , Gomis Xavier , Ramírez José Luis , Azuaje Carlos , Almirante Benito , Pahissa Albert 
Published: July 2002

ABSTRACT

We compared the efficacy of ceftriaxone combined with gentamicin, both given once a day, with that of cloxacillin given every 4 h plus gentamicin given once a day or in three daily doses (t.i.d.) for the treatment of experimental methicillin-susceptible staphylococcal endocarditis. The antibiotics were administered by using human-like (H-L) pharmacokinetics that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 10
5
CFU of
Staphylococcus aureus
S5 (MICs and minimal bactericidal concentrations of cloxacillin, ceftriaxone, and gentamicin, 0.5 and 2 μg/ml, 4 and 8 μg/ml, and 0.5 and 1 μg/ml, respectively). The animals were then treated for 24 h with cloxacillin at a dose of 2 g that simulated H-L pharmacokinetics (H-L 2 g) every 4 h alone or combined with gentamicin (administered at doses of H-L 1 mg/kg of body weight every 8 h or H-L 4.5 mg/kg every 24 h) or with ceftriaxone at H-L 2 g every 24 h alone or combined with gentamicin (administered at doses of H-L 1 mg/kg every 8 h or H-L 4.5 mg/kg every 24 h). The results of therapy for experimental endocarditis due to the S5 strain showed that (i) cloxacillin alone is more effective than ceftriaxone alone in reducing the bacterial load (
P
< 0.01), (ii) the combination of cloxacillin or ceftriaxone with gentamicin is more effective than each of these drugs alone (
P
< 0.01), and (iii) Ceftriaxone H-L plus gentamicin H-L 4.5 mg/kg, both administered every 24 h, showed efficacy similar to that of the “gold standard,” cloxacillin H-L plus gentamicin H-L 1 mg/kg t.i.d. (
P
> 0.05). An increase in the interval of administration of gentamicin to once daily resulted in a reduction in the numbers of bacteria in the vegetations equivalent to that achieved with the recommended regimen of cloxacillin plus gentamicin t.i.d. in the treatment of experimental endocarditis due to methicillin-susceptible
S. aureus
. Ceftriaxone plus gentamicin, both administered once a day, may be useful for home-based therapy for selected cases of staphylococcal endocarditis.
Expression of
lux
Genes in a Clinical Isolate of
Streptococcus pneumoniae
: Using Bioluminescence To Monitor Gemifloxacin Activity
Authors: Beard S. J. , Salisbury V. , Lewis R. J. , Sharpe J. A. , MacGowan A. P. 
Published: July 2002

ABSTRACT

A clinical isolate of
Streptococcus pneumoniae
was transformed with a plasmid containing the
lux
operon of
Photorhabdus luminescens
that had been modified to function in gram-positive bacteria. Cells containing this plasmid produced light stably and constitutively, without compromising the growth rate. Light output was correlated with measurements of optical density and viable counts during exponential growth and provided a sensitive, real-time measure of the pharmacodynamics of the fluoroquinolone gemifloxacin.
Susceptibility to Telithromycin in 1,011
Streptococcus pyogenes
Isolates from 10 Central and Eastern European Countries
Authors: Nagai Kensuke , Appelbaum Peter C. , Davies Todd A. , Kelly Linda M. , Hoellman Dianne B. , Andrasevic Arjana Tambic , Drukalska Liga , Hryniewicz Waleria , Jacobs Michael R. , Kolman Jana , Miciuleviciene Jolanta , Pana Marina , Setchanova Lena , Thege Marianne Konkoly , Hupkova Helena , Trupl Jan , Urbaskova Pavla 
Published: July 2002

ABSTRACT

Among 1,011 recently isolated
Streptococcus pyogenes
isolates from 10 Central and Eastern European centers, the MICs at which 50% of isolates are inhibited (MIC
50
s) and the MIC
90
s were as follows: for telithromycin, 0.03 and 0.06 μg/ml, respectively; for erythromycin, azithromycin, and clarithromycin, 0.06 to 0.125 and 1 to 8 μg/ml, respectively; and for clindamycin, 0.125 and 0.125 μg/ml, respectively. Erythromycin resistance occurred in 12.3% of strains.
Erm
(A) [subclass
erm
(TR)] was most commonly encountered (60.5%), followed by
mef
(A) (23.4%) and
erm
(B) (14.5%). At <0.5 μg/ml, telithromycin was active against 98.5% of the strains tested.
Ribosomal Mutations in
Streptococcus pneumoniae
Clinical Isolates
Authors: Pihlajamäki Marja , Kataja Janne , Seppälä Helena , Elliot John , Leinonen Maija , Huovinen Pentti , Jalava Jari 
Published: July 2002

ABSTRACT

Eleven clinical isolates of
Streptococcus pneumoniae
, isolated in Finland during 1996 to 2000, had an unusual macrolide resistance phenotype. They were resistant to macrolides and streptogramin B but susceptible, intermediate, or low-level resistant to lincosamides. No acquired macrolide resistance genes were detected from the strains. The isolates were found to have mutations in domain V of the 23S rRNA or ribosomal protein L4. Seven isolates had an A2059C mutation in two to four out of the four alleles encoding the 23S rRNA, two isolates had an A2059G mutation in two alleles, one isolate had a C2611G mutation in all four alleles, and one isolate had a
69
GTG
71
-to-
69
TPS
71
substitution in ribosomal protein L4.
Characterization of a New Extended-Spectrum β-Lactamase (TEM-87) Isolated in
Proteus mirabilis
during an Italian Survey
Authors: Perilli Mariagrazia , Segatore Bernardetta , Massis Maria Rosaria De , Franceschini Nicola , Bianchi Ciro , Rossolini Gian Maria , Amicosante Gianfranco 
Published: July 2002

ABSTRACT

A new natural TEM derivative, named TEM-87, was identified in a
Proteus mirabilis
isolate from an Italian hospital. Compared to TEM-1, TEM-87 contains the following mutations: E104K, R164C, and M182T. Kinetic analysis of TEM-87 revealed extended-spectrum activity against oxyimino cephalosporins (preferentially ceftazidime) and aztreonam. Expression of
bla
TEM-87
in
Escherichia coli
decreased the host susceptibility to these drugs.
In Vitro Antifungal Susceptibilities of
Trichosporon
Species
Authors: Paphitou Niki I. , Ostrosky-Zeichner Luis , Paetznick Victor L. , Rodriguez Jose R. , Chen Enuo , Rex John H. 
Published: July 2002

ABSTRACT

The in vitro activities of amphotericin B, itraconazole, fluconazole, voriconazole, posaconazole, and ravuconazole against 39 isolates of
Trichosporon
spp. were determined by the NCCLS M27-A microdilution method. The azoles tested appeared to be more potent than amphotericin B. Low minimal fungicidal concentration/MIC ratios were observed for voriconazole, posaconazole, and ravuconazole, suggesting fungicidal activity.
In Vitro and In Vivo Activities of Anti-Influenza Virus Compound T-705
Authors: Furuta Y. , Takahashi K. , Fukuda Y. , Kuno M. , Kamiyama T. , Kozaki K. , Nomura N. , Egawa H. , Minami S. , Watanabe Y. , Narita H. , Shiraki K. 
Published: July 2002

ABSTRACT

T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has been found to have potent and selective inhibitory activity against influenza virus. In an in vitro plaque reduction assay, T-705 showed potent inhibitory activity against influenza A, B, and C viruses, with 50% inhibitory concentrations (IC
50
s) of 0.013 to 0.48 μg/ml, while it showed no cytotoxicity at concentrations up to 1,000 μg/ml in Madin-Darby canine kidney cells. The selectivity index for influenza virus was more than 2,000. It was also active against a neuraminidase inhibitor-resistant virus and some amantadine-resistant viruses. T-705 showed weak activity against non-influenza virus RNA viruses, with the IC
50
s being higher for non-influenza virus RNA viruses than for influenza virus, and it had no activity against DNA viruses. Orally administered T-705 at 100 mg/kg of body weight/day (four times a day) for 5 days significantly reduced the mean pulmonary virus yields and the rate of mortality in mice infected with influenza virus A/PR/8/34 (3 × 10
2
PFU). These results suggest that T-705 may be a compound that is useful and highly selective against influenza virus infections and that has a mode of action different from those of commercially available drugs, such as amantadine, rimantadine, and neuraminidase inhibitors.
Anti-Human Immunodeficiency Virus Interactions of SCH-C (SCH 351125), a CCR5 Antagonist, with Other Antiretroviral Agents In Vitro
Authors: Tremblay Cécile L. , Giguel Françoise , Kollmann Christopher , Guan Yongbiao , Chou Ting-Chao , Baroudy Bahige M. , Hirsch Martin S. 
Published: July 2002

ABSTRACT
SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses.