bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Anti-
Helicobacter pylori
Activities of New Rifamycin Derivatives, KRM-1648 and KRM-1657
Authors: Akada Junko K. , Shirai Mutsunori , Fujii Kenji , Okita Kiwamu , Nakazawa Teruko 
Published: October 2018

ABSTRACT

The new rifamycin derivatives KRM-1657 and KRM-1648 were evaluated for their in vitro antimicrobial activities against 44 strains of
Helicobacter pylori
. Although the drugs were not very active against other gram-negative bacteria, the MICs at which 90% of isolates are inhibited for these drugs were lower (0.002 and 0.008 μg/ml, respectively) than those of amoxicillin and rifampin for
H. pylori
. Time-kill studies revealed that the bactericidal activities of these agents were due to cell lysis. The results presented here indicate that these new rifamycin derivatives may be useful for the eradication of
H. pylori
infections.
In Vitro and In Vivo Antimicrobial Activities of T-3811ME, a Novel Des-F(6)-Quinolone
Authors: Takahata Masahiro , Mitsuyama Junichi , Yamashiro Yoshiko , Yonezawa Minoru , Araki Harumi , Todo Yozo , Minami Shinzaburo , Watanabe Yasuo , Narita Hirokazu 
Published: October 2018

ABSTRACT

The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against
Chlamydia trachomatis
,
Mycoplasma pneumoniae
, and
Mycobacterium tuberculosis
. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC
90
s) of 0.025 to 6.25 μg/ml. T-3811 was the most active agent against methicillin-resistant
Staphylococcus aureus
and streptococci, including penicillin-resistant
Streptococcus pneumoniae
(PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family
Enterobacteriaceae
and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against
Haemophilus influenzae
,
Moraxella catarrhalis
, and
Legionella
sp., with MIC
90
s of 0.0125 to 0.1 μg/ml. T-3811 showed a potent activity against anaerobic bacteria, such as
Bacteroides fragilis
and
Clostridium difficile
. T-3811 was the most active agent against
C. trachomatis
(MIC, 0.008 μg/ml) and
M. pneumoniae
(MIC
90
, 0.0313 μg/ml). The activity of T-3811 against
M. tuberculosis
(MIC
90
, 0.0625 μg/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of
S. aureus
and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.
Efficacy of Microencapsulated Rifampin in
Mycobacterium tuberculosis
-Infected Mice
Authors: Quenelle Debra C. , Staas Jay K. , Winchester Gary A. , Barrow Esther L. W. , Barrow William W. 
Published: October 2018

ABSTRACT

Rifampin is a first-line drug useful in the treatment of tuberculosis. By using biocompatible polymeric excipients of lactide and glycolide copolymers, two microsphere formulations were developed for targeted and sustained delivery of rifampin, with minimal dosing. A small-microsphere formulation, with demonstrated ability to inhibit intracellularly replicating
Mycobacterium tuberculosis
H37Rv, was tested along with a large-microsphere formulation in an infected mouse model. Results revealed that by using a single treatment of the large-microsphere formulation, it was possible to achieve a significant reduction in
M. tuberculosis
H37Rv CFUs in the lungs of mice by 26 days postinfection. A combination of small (given as two injections on day 0 and day 7) and large (given as one injection at day 0) rifampin-loaded microsphere formulations resulted in significant reductions in CFUs in the lungs by 26 days, achieving a 1.23 log
10
reduction in CFUs. By comparison, oral treatment with 5, 10, or 20 mg of rifampin/kg of body weight, administered every day, resulted in a reduction of 0.42, 1.7, or 1.8 log
10
units, respectively. Thus the microsphere formulations, administered in one or two doses, were able to achieve results in mice similar to those obtained with a daily drug regimen within the range of the highest clinically tolerated dosage in humans. These results demonstrate that microsphere formulations of antimycobacterial drugs such as rifampin can be used for therapy of tuberculosis with minimal dosing.
Mechanism of the Intracellular Killing and Modulation of Antibiotic Susceptibility ofListeria monocytogenesin THP-1 Macrophages Activated by Gamma Interferon
Authors: Ouadrhiri Youssef , Scorneaux Bernard , Sibille Yves , Tulkens Paul M. 
Published: October 2018

ABSTRACTListeria monocytogenes, a facultative intracellular pathogen, readily enters cells and multiplies in the cytosol after escaping from phagosomal vacuoles. Macrophages exposed to gamma interferon, one of the main cellular host defenses againstListeria, become nonpermissive for bacterial growth while containingListeriain the phagosomes. Using the human myelomonocytic cell line THP-1, we show that the combination ofl-monomethyl arginine and catalase restores bacterial growth without affecting the phagosomal containment ofListeria. A previous report (B. Scorneaux, Y. Ouadrhiri, G. Anzalone, and P. M. Tulkens, Antimicrob. Agents Chemother. 40:1225–1230, 1996) showed that intracellularListeriawas almost equally sensitive to ampicillin, azithromycin, and sparfloxacin in control cells but became insensitive to ampicillin and more sensitive to azithromycin and sparfloxacin in gamma interferon-treated cells. We show here that these modulations of antibiotic activity are largely counteracted byl-monomethyl arginine and catalase. In parallel, we show that gamma interferon enhances the cellular accumulation of azithromycin and sparfloxacin, an effect which is not reversed by addition ofl-monomethyl arginine and catalase and which therefore cannot account for the increased activity of these antibiotics in gamma interferon-treated cells. We conclude that (i) the control exerted by gamma interferon on intracellular multiplication ofListeriain THP-1 macrophages is dependent on the production of nitric oxide and hydrogen peroxide; (ii) intracellularListeriamay become insensitive to ampicillin in macrophages exposed to gamma interferon because the increase in reactive oxygen and nitrogen intermediates already controls bacterial growth; and (iii) azithromycin and still more sparfloxacin cooperate efficiently with gamma interferon, one of the main cellular host defenses inListeriainfection.
Comparison of In Vitro Activity of Liposomal Nystatin against
Aspergillus
Species with Those of Nystatin, Amphotericin B (AB) Deoxycholate, AB Colloidal Dispersion, Liposomal AB, AB Lipid Complex, and Itraconazole
Authors: Oakley Karen L. , Moore Caroline B. , Denning David W. 
Published: October 2018

ABSTRACT

We compared the in vitro activity of liposomal nystatin (Nyotran) with those of other antifungal agents against 60
Aspergillus
isolates. Twelve isolates were itraconazole resistant. For all isolates, geometric mean (GM) MICs (micrograms per milliliter) were 2.30 for liposomal nystatin, 0.58 for itraconazole, 0.86 for amphotericin B (AB) deoxycholate, 9.51 for nystatin, 2.07 for liposomal AB, 2.57 for AB lipid complex, and 0.86 for AB colloidal dispersion.
Aspergillus terreus
(GM, 8.72 μg/ml; range, 8 to 16 μg/ml) was significantly less susceptible to all of the polyene drugs than all other species (
P
= 0.0001).
An SHV-Derived Extended-Spectrum β-Lactamase in
Pseudomonas aeruginosa
Authors: Naas Thierry , Philippon Laurence , Poirel Laurent , Ronco Esthel , Nordmann Patrice 
Published: October 2018

ABSTRACT

A clinical isolate of
Pseudomonas aeruginosa
RP-1 produced the extended-spectrum β-lactamase (ESBL) SHV-2a. Its gene was expressed from a composite promoter made of the −35 region derived from the left inverted repeat of IS
26
and the −10 region from the
bla
SHV-2a
promoter itself. The DNA sequences immediately surrounding
bla
SHV-2a
were homologous to plasmid pMPA2a from
Klebsiella pneumoniae
KpZU-3, while further away and 3′ to the
bla
SHV-2a
gene, a sequence corresponding to the left end of Tn
1721
was detected, thus indicating a likely enterobacterial origin of this ESBL gene.
Antimicrobial Activities and Postantibiotic Effects of Clarithromycin, 14-Hydroxy-Clarithromycin, and Azithromycin in Epithelial Cell Lining Fluid against Clinical Isolates ofHaemophilus influenzaeandStreptococcus pneumoniae
Authors: Bergman Kimberly L. , Olsen Keith M. , Peddicord Tom E. , Fey Paul D. , Rupp Mark E. 
Published: October 2018

ABSTRACTThe antimicrobial activity of concentrations of selected macrolides found in epithelial cell lining fluid was investigated. Clarithromycin demonstrated greater potency and a significantly longer postantibiotic effect (PAE) than azithromycin againstStreptococcus pneumoniae. Azithromycin displayed greater potency, faster killing, and a longer PAE than clarithromycin againstHaemophilus influenzae. Drug concentrations in epithelial cell lining fluid similar to those found in tissue did not improve the synergistic potential of 14-hydroxy-clarithromycin and indicate that a maximal PAE may exist despite increasing concentrations of drug.
Sensitivity of Spermidine-Deficient
Saccharomyces cerevisiae
to Paromomycin
Authors: Balasundaram David , Tabor Celia White , Tabor Herbert 
Published: October 2018

ABSTRACT

Spermidine-deficient
Saccharomyces cerevisiae
cells are much more sensitive to paromomycin than nondeficient cells, resulting in cessation of growth and cell death.
Amphotericin B in Children with Malignant Disease: a Comparison of the Toxicities and Pharmacokinetics of Amphotericin B Administered in Dextrose versus Lipid Emulsion
Authors: Nath Christa E. , Shaw Peter J. , Gunning Robyn , McLachlan Andrew J. , Earl John W. 
Published: October 2018

ABSTRACT

In a prospective, randomized clinical trial, the toxicity of 1 mg of amphotericin B (AmB) per kg of body weight per day infused in 5% dextrose was compared with that of AmB infused in lipid emulsion in children with malignant disease. In an analysis of 82 children who received a full course of 6 days or more of AmB (117 courses), it was shown that there were significant increases in plasma urea and creatinine concentrations and in potassium requirement after 6 days of therapy with both AmB infused in dextrose and AmB infused in lipid emulsion, with there being no difference between the two methods of AmB administration. An intent-to-treat comparison of the numbers of courses affected by acute toxicity (fever, rigors) and chronic toxicity (nephrotoxicity) also indicated that there was no significant difference between AmB infused in dextrose (78 courses) and AmB infused in lipid emulsion (84 courses). The pharmacokinetics of AmB were investigated in 20 children who received AmB in dextrose and 15 children who received AmB in lipid emulsion. Blood samples were collected up to 24 h after administration of the first dose, and the concentration of AmB in plasma was analyzed by a high-performance liquid chromatography assay. The clearance (CL) of AmB in dextrose (0.039 ± 0.016 liter · h
−1
· kg
−1
) was significantly lower (
P
< 0.005) than the CL of AmB in lipid emulsion (0.062 ± 0.024 liter · h
−1
· kg
−1
). The steady-state volume of distribution for AmB in dextrose (0.83 ± 0.33 liter · kg
−1
) was also significantly lower (
P
< 0.005) than that for AmB in lipid emulsion (1.47 ± 0.77 liter · kg
−1
). Although AmB in lipid emulsion is apparently cleared faster and distributes more widely than AmB in dextrose, this study did not reveal any significant advantage with respect to safety and tolerance in the administration of AmB in lipid emulsion compared to its administration in dextrose in children with malignant disease.
Azithromycin versus Ciprofloxacin for Treatment of Uncomplicated Typhoid Fever in a Randomized Trial in Egypt That Included Patients with Multidrug Resistance
Authors: Girgis Nabil I. , Butler Thomas , Frenck Robert W. , Sultan Yehia , Brown Forrest M. , Tribble David , Khakhria Rasik 
Published: October 2018

ABSTRACT

To compare clinical and bacteriological efficacies of azithromycin and ciprofloxacin for typhoid fever, 123 adults with fever and signs of uncomplicated typhoid fever were entered into a randomized trial. Cultures of blood were positive for
Salmonella typhi
in 59 patients and for
S. paratyphi
A in 3 cases; stool cultures were positive for
S. typhi
in 11 cases and for
S. paratyphi
A in 1 case. Multiple-drug resistance (MDR; resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole) was present in isolates of 21 of 64 patients with positive cultures. Of these 64 patients, 36 received 1 g of azithromycin orally once on the first day, followed by 500 mg given orally once daily on the next 6 days; 28 patients received 500 mg of ciprofloxacin orally twice daily for 7 days. Blood cultures were repeated on days 4 and 10 after the start of therapy, and stool cultures were done on days 4, 10, and 28 after the start of therapy. All patients in both groups improved during therapy and were cured. Defervescence (maximum daily temperatures of ≤38°C) occurred at the following times [mean ± standard deviation (range)] after the start of therapy: 3.8 ± 1.1 (2 to 7) days with azithromycin and 3.3 ± 1.0 (1 to 5) days with ciprofloxacin. No relapses were detected. Cultures of blood and stool during and after therapy were negative in all cases, except for one patient treated with azithromycin who had a positive blood culture on day 4. These results indicated that azithromycin and ciprofloxacin were similarly effective, both clinically and bacteriologically, against typhoid fever caused by both sensitive organisms and MDR
S. typhi
.
In Vitro Susceptibilities of
Candida
and
Cryptococcus neoformans
Isolates from Blood Cultures of Neutropenic Patients
Authors: Hoban Daryl J. , Zhanel George G. , Karlowsky James A. 
Published: October 2018

ABSTRACT

Fluconazole-resistant
Candida albicans
and intrinsically fluconazole-resistant
Candida
species have been reported as bloodstream isolates. However, an association between the isolation of fluconazole-resistant
Candida
from the bloodstream and patient risk factors for fungemia has not been established. The purpose of this study was to determine the prevalence of fluconazole resistance in bloodstream isolates of
Candida
species and
Cryptococcus neoformans
collected from patients with neutropenia, one of the most important risk factors for fungemia. MICs of voriconazole, fluconazole, itraconazole, ketoconazole, amphotericin B, and flucytosine were determined by the National Committee for Clinical Laboratory Standards M27-A method (1997). Voriconazole, on a per-weight basis, was the most active azole tested. Fluconazole resistance (MIC ≥ 64 μg/ml) was not identified in any of the
C. albicans
(
n
= 513),
Candida parapsilosis
(
n
= 78),
Candida tropicalis
(
n
= 62), or
C. neoformans
(
n
= 38) isolates tested.
Linezolid Activity Compared to Those of Selected Macrolides and Other Agents against Aerobic and Anaerobic Pathogens Isolated from Soft Tissue Bite Infections in Humans
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni 
Published: October 2018

ABSTRACTLinezolid was tested against 420 aerobes and anaerobes, including 148Pasteurellaisolates, by an agar dilution method. Linezolid was active against allPasteurella multocidasubsp.multocidaandP. multocidasubsp.septicaisolates and mostPasteurella canis,Pasteurella dagmatis, andPasteurella stomatisisolates. The MIC was ≤2 μg/ml for staphylococci, streptococci, EF-4b,Weeksella zoohelcum,Fusobacterium nucleatum, other fusobacteria,Porphyromonasspp.,Prevotellaspp., peptostreptococci, and almost allBacteroides tectumisolates.
Effect of Azithromycin plus Rifampin versus That of Azithromycin Alone on the Eradication of
Chlamydia pneumoniae
from Lung Tissue in Experimental Pneumonitis
Authors: Wolf Katerina , Malinverni Raffaele 
Published: October 2018

ABSTRACT

Azithromycin, doxycycline, and rifampin, alone or in combination, were tested in vitro against
Chlamydia pneumoniae
AR-39. The combination of azithromycin plus rifampin showed the strongest activity and produced higher rates of eradication of
C. pneumoniae
from lung tissues than azithromycin alone in experimental mouse pneumonitis.
Salt-Resistant Alpha-Helical Cationic Antimicrobial Peptides
Authors: Friedrich Carol , Scott Monisha G. , Karunaratne Nedra , Yan Hong , Hancock Robert E. W. 
Published: October 2018

ABSTRACT

Analogues based on the insect cecropin–bee melittin hybrid peptide (CEME) were studied and analyzed for activity and salt resistance. The new variants were designed to have an increase in amphipathic α-helical content (CP29 and CP26) and in overall positive charge (CP26). The α-helicity of these peptides was demonstrated by circular dichroism spectroscopy in the presence of liposomes. CP29 was shown to have activity against gram-negative bacteria that was similar to or better than those of the parent peptides, and CP26 had similar activity. CP29 had cytoplasmic membrane permeabilization activity, as assessed by the unmasking of cytoplasmic β-galactosidase, similar to that of CEME and its more positively charged derivative named CEMA, whereas CP26 was substantially less effective. The activity of the peptides was not greatly attenuated by an uncoupler of membrane potential, carbonyl cyanide-
m
-chlorophenylhydrazone. The tryptophan residue in position 2 was shown to be necessary for interaction with cell membranes, as demonstrated by a complete lack of activity in the peptide CP208. Peptides CP29, CEME, and CEMA were resistant to antagonism by 0.1 to 0.3 M NaCl; however, CP26 was resistant to antagonism only by up to 160 mM NaCl. The peptides were generally more antagonized by 3 and 5 mM Mg
2+
and by the polyanion alginate. It appeared that the positively charged C terminus in CP26 altered its ability to permeabilize the cytoplasmic membrane of
Escherichia coli
, although CP26 maintained its ability to kill gram-negative bacteria. These peptides are potential candidates for future therapeutic drugs.
Pharmacokinetics of Dirithromycin in Patients with Mild or Moderate Cirrhosis
Authors: Mazzei Teresita , Surrenti Calogero , Novelli Andrea , Biagini Maria Rosa , Fallani Stefania , Cassetta Maria Iris , Conti Silvia , Surrenti Elisabetta 
Published: October 2018

ABSTRACT

The pharmacokinetics of dirithromycin were determined over a 72-h period following oral administration of a single 500-mg dose to 8 healthy volunteers and to 16 cirrhotic patients (8 patients with class A cirrhosis and 8 patients with class B cirrhosis according to Pugh’s & Child’s classification). Drug levels in plasma and urine were determined by microbiological assay. The mean maximum concentrations of drug in serum obtained 3 to 4 h after administration were 0.29 ± 0.22 mg/liter in volunteers and 0.48 ± 0.21 and 0.52 ± 0.38 mg/liter in patients with class A and class B cirrhosis, respectively. The elimination half-life (
t
1/2β
) was 23.3 ± 7.6 h in healthy subjects and 35.2 ± 11.8 h and 39.5 ± 11.0 h in patients with class A and class B cirrhosis, respectively. The mean area under the concentration-time curve (AUC) and
t
1/2β
were significantly higher in patients with class A and B cirrhosis than in healthy controls, while total and renal clearances were markedly reduced (
P
< 0.01). The time to the maximum concentration of drug in serum and the volume of distribution values appeared to be similar in all groups, and the mean recovery in urine at 72 h ranged from 3.7 to 5.7%, without significant differences among groups. These results demonstrate that some dirithromycin kinetic parameters are significantly different in cirrhotic patients in comparison to those in healthy volunteers. However, an increase in the
t
1/2β
or AUC, which is also observed with other semisynthetic macrolides (e.g., azithromycin), does seem to be not clinically relevant if one takes into account both the high therapeutic indices of these antibiotics and the usually short duration of therapy. Therefore, on the limited basis of single-dose administration, no modifications of dirithromycin dosage seem to be required even for patients with class B liver cirrhosis.
Cloning and Characterization of a Gene,
pbpF
, Encoding a New Penicillin-Binding Protein, PBP2B, in
Staphylococcus aureus
Authors: Komatsuzawa Hitoshi , Choi Gil H. , Ohta Kouji , Sugai Motoyuki , Tran Monique T. , Suginaka Hidekazu 
Published: October 2018

ABSTRACT

A previously unrecognized penicillin binding protein (PBP) gene,
pbpF
, was identified in
Staphylococcus aureus
. This gene encodes a protein of 691 amino acid residues with an estimated molecular mass of 78 kDa. The molecular mass is very close to that of
S. aureus
PBP2 (81 kDa), and the protein is tentatively named PBP2B. PBP2B has three motifs, SSVK, SSN, and KTG, that can be found in PBPs and β-lactamases. Recombinant PBP2B (rPBP2B), which lacks a putative signal peptide at the N terminus and has a histidine tag at the C terminus, was expressed in
Escherichia coli
. The purified rPBP2B was shown to have penicillin binding activity. A protein band was detected from
S. aureus
membrane fraction by immunoblotting with anti-rPBP2B serum. Also, penicillin binding activity of the protein immunoprecipitated with anti-rPBP2B serum was detected. These results suggest the presence of PBP2B in
S. aureus
cell membrane that covalently binds penicillin. The internal region of
pbpF
and PBP2B protein were found in all 12
S. aureus
strains tested by PCR and immunoblotting.
Use of Real-Time PCR and Fluorimetry To Detect Lamivudine Resistance-Associated Mutations in Hepatitis B Virus
Authors: Cane Patricia A. , Cook Pamela , Ratcliffe Daina , Mutimer David , Pillay Deenan 
Published: October 2018

ABSTRACTVery rapid amplification of DNA by PCR in small volumes can be continuously monitored by the detection of the binding of probes with a rapid cycler with built-in fluorometric detection. Primers were designed to amplify approximately 100 bp of the polymerase gene of hepatitis B virus (HBV) spanning codon 550, where mutations associated with resistance to lamivudine invariably occur. Four hybridization probes were synthesized: one was 3′ labelled with fluorescein and hybridized upstream of codon 550. The others were 5′ labelled with Cy5 and 3′ labelled with biotin and spanned codon 550. The Cy5-labelled oligonucleotides contained either wild-type (ATG) or mutant (GTG or ATT) sequences. A Cy5-labelled probe and either the fluorescein-labelled probe or Sybr Green 1 (a compound that fluoresces when bound to double-stranded DNA) were included in each PCR. After completion of the amplification by using a LightCycler (Idaho Technology), the temperature at which the Cy5 probe melted from the product was determined in a melt program that took ca. 3 min. Pre- and posttreatment samples from eight patients (five chronic and three transplant) who failed lamivudine treatment were amplified, and the presence of mutations in codon 550 was determined by ABI sequencing and by using the LightCycler; in some cases PCR products were also cloned, and multiple clones were sequenced. Concordant results were obtained in all cases. We found the LightCycler to be better at resolving the sequences of genomic mixtures; for example, two samples showed a sequence at codon 550 of (A/G)T(G/T), which was found by fluorimetry to be mixtures of GTG and ATT but no ATG, and this finding was confirmed by the sequencing of clones. However, this approach was not more sensitive than population sequencing for the detection of the presence of mixtures. Overall, this pilot study has demonstrated an approach that could be an extremely rapid and economical method for the detection of lamivudine resistance-associated mutations in HBV.