bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Community-Acquired Acute Uncomplicated Urinary Tract Infection with Sparfloxacin versus Ofloxacin
Authors: Henry D. , Ellison W. , Sullivan J. , Mansfield D. L. , Magner D. J. , Dorr M. B. , Talbot G. H. , Group For The Sparfloxacin Multicenter Uuti Study 
Published: October 2018

ABSTRACTThe efficacy and safety of a 3-day regimen of sparfloxacin were compared with those of a 3-day regimen of ofloxacin for the treatment of community-acquired acute uncomplicated urinary tract infections. Four hundred nineteen women were enrolled in a randomized, open-label, observer-blinded, multicenter study; 204 received sparfloxacin as a 400-mg loading dose on the first day and 200 mg once daily thereafter, and 215 received ofloxacin as 200 mg twice daily. A total of 383 patients met the criteria for clinical evaluability, and 174 were also bacteriologically evaluable; all treated patients were included in the safety analysis.Escherichia coli(86%) andStaphylococcus saprophyticus(4.6%) were the organisms most commonly isolated. Positive clinical responses were obtained 5 to 9 days after therapy in more than 92% of the patients in each group; sustained clinical cure rates 4 to 6 weeks after therapy were 78.3 and 76.9% in the sparfloxacin and ofloxacin groups, respectively. A positive bacteriologic response was observed in 98% of the bacteriologically evaluable patients in each treatment group at 5 to 9 days posttherapy and in 88.2 and 92.6% of the patients in the sparfloxacin and ofloxacin groups, respectively, 4 to 6 weeks after therapy. Almost 90% of all adverse events were of mild or moderate severity; the most frequent events at least possibly related to drug treatment were those common to the fluoroquinolones, namely, nausea, diarrhea, headache, insomnia, and photosensitivity. Photosensitivity was more frequent in the sparfloxacin group (6.9% versus 0.5% in the ofloxacin group); insomnia was more frequent in the ofloxacin group (3.7% versus 1.0% in the sparfloxacin group). These data suggest that a once-daily, 3-day regimen of sparfloxacin is effective and generally well tolerated in the treatment of acute uncomplicated urinary tract infections.
Identification of Elongation Factor 2 as the Essential Protein Targeted by Sordarins in
Candida albicans
Authors: Domínguez Juan Manuel , Martín J. Julio 
Published: October 2018

ABSTRACT

The target for sordarins in
Candida albicans
has been elucidated. Kinetic experiments of sordarin inhibition as well as displacement experiments showed that the formation of a sordarin-target complex follows a reversible mechanism. Binding of tritiated drug to the target is enhanced in the presence of ribosomes. Isolation of the target by classical protein purification methods has allowed us to identify it as elongation factor 2. This is in agreement with the nature of sordarin derivatives as specific inhibitors of the elongation cycle within protein synthesis in yeasts.
Inhibition of Tumor Necrosis Factor Alpha Alters Resistance toMycobacterium aviumComplex Infection in Mice
Authors: Bala Shukal , Hastings Kenneth L. , Kazempour Kazem , Inglis Shelly , Dempsey Walla L. 
Published: October 2018

ABSTRACTIncreased production of tumor necrosis factor alpha (TNF-α) appears to play an important role in the progression of human immunodeficiency virus disease. One treatment strategy being explored is the use of TNF-α inhibitors. TNF-α also appears to be important in conferring resistance to infections, and the inhibition of this cytokine may exacerbate the emergence of opportunistic pathogens, such asMycobacterium aviumcomplex (MAC). The present study examines the possibility that inhibition of TNF-α will increase the progression of disease in mice infected with MAC. C57BL/6 beige (bg/bg) mice have been shown to be highly susceptible to infection with MAC and are routinely used for testing of antimycobacterial drugs. However,bg/bgmice are known to exhibit impaired phagocyte and natural killer cell function. Since these cell types are important sources of TNF-α, the susceptibility of thebg/bgstrain to infection with MAC was compared with those of the heterozygous (bg/+) and wild-type (+/+) strains of C57BL/6 mice. The susceptibilities of thebg/bgandbg/+ strains of mice infected with MAC were found to be comparable. The +/+ strain was the least susceptible. Mycobacterial burden and serum TNF-α levels increased over time in all the strains of mice tested. Thebg/+ strain of C57BL/6 mice was then chosen to measure the activity of TNF-α antagonists. Treatment with dexamethasone decreased serum TNF-α levels and increased mycobacterial burden. Treatment with anti-TNF-α antibody or pentoxifylline did not significantly alter serum TNF-α levels but increased mycobacterial burden. Treatment with thalidomide neither consistently altered mycobacterial burden in the spleens or livers of infected mice nor affected serum TNF-α levels.
Absence of Effect of Rufloxacin on Theophylline Pharmacokinetics in Steady State
Authors: Kinzig-Schippers Martina , Fuhr Uwe , Cesana Marina , Müller Carola , Staib A. Horst , Rietbrock S. , Sörgel Fritz 
Published: October 2018

ABSTRACT
Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration. A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline. Both drugs were administered at steady state. Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only. During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction. Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods. To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period. These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1.02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05). In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state. Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events.
In Vitro Pharmacodynamic Studies of L-749,345 in Comparison with Imipenem and Ceftriaxone against Gram-Positive and Gram-Negative Bacteria
Authors: Odenholt Inga , Löwdin Elisabeth , Cars Otto 
Published: October 2018

ABSTRACT

L-749,345 is a new parenteral carbapenem with a very long half-life similar to that of ceftriaxone. The aim of the present study was to investigate different pharmacodynamic parameters of L-749,345 in comparison with those of ceftriaxone and imipenem. The following studies were performed: (i) comparative studies of the MICs of L-749,345, imipenem, and ceftriaxone for 70 strains of gram-positive and gram-negative bacteria; (ii) comparative studies of the rate of killing of gram-positive and gram-negative bacteria by L-749,345, imipenem, and ceftriaxone; (iii) studies of the postantibiotic effects of L-749,345, imipenem, and ceftriaxone; and (iv) studies of the postantibiotic sub-MIC effects of L-749,345, imipenem, and ceftriaxone. Significantly lower MICs of L-749,345 compared with those of ceftriaxone were found for all gram-negative organisms except
Haemophilus influenzae
. The MICs of L-749,345 were similar to those of imipenem for all organisms except
Pseudomonas aeruginosa
and methicillin-resistant
Staphylococcus aureus
, for which the MICs of L-749,345 were higher. A concentration-dependent killing of methicillin-resistant
S. aureus
but not methicillin-susceptible strains was noted for both L-749,345 and imipenem. All three of the investigated drugs exhibited a postantibiotic effect against the gram-positive strains but exhibited no postantibiotic effect against the gram-negative strains.
Efficacy of Nikkomycin Z in the Treatment of Murine Histoplasmosis
Authors: Graybill John R. , Najvar Laura K. , Bocanegra Rosie , Hector Richard F. , Luther Michael F. 
Published: October 2018

ABSTRACT

Immune-competent ICR and BALB/c athymic (nude) mice were infected intravenously with
Histoplasma capsulatum
and treated with either fluconazole or nikkomycin Z or 5% dextrose (controls). In immune-competent ICR mice, fluconazole and nikkomycin Z both prolonged survival when given at 5 mg/kg of body weight twice daily. When administered in doses as low as 2.5 mg/kg twice daily, nikkomycin Z reduced fungal counts in both the spleen and liver. When both drugs were combined, there was no antagonism, and in combined therapy spleen and liver counts were reduced more than for either drug alone. However, nikkomycin Z had no effect on brain fungal burden. In nude mice fluconazole and nikkomycin Z had an additive effect in prolongation of survival and reduction of liver and spleen burden. Nikkomycin Z is well tolerated, is at least as effective as fluconazole, and may interact beneficially with fluconazole for treatment of murine histoplasmosis.
Superior Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in the Treatment of Severe Candidiasis in Leukopenic Mice
Authors: van Etten Els W. M. , Snijders Susan V. , van Vianen Wim , Bakker-Woudenberg Irma A. J. M. 
Published: October 2018

ABSTRACT

In leukopenic mice with severe systemic candidiasis, single-dose treatment (5 mg of amphotericin B [AMB]/kg of body weight) with long-circulating polyethylene glycol-coated AMB liposomes (PEG-AMB-LIP) resulted in zero mortality and a significant reduction in the number of viable
Candida albicans
in the kidney, whereas 70% mortality was seen in mice treated with five daily doses of AmBisome (5 mg of AMB/kg · day). When the first of five daily doses of AmBisome was combined with a single low dose of Fungizone (0.1 mg of AMB/kg), the efficacy was equal to that of PEG-AMB-LIP.
Microbicidal Activity of a New Silver-Containing Polymer, SPI-ARGENT II
Authors: Kampf Günter , Dietze Beate , Große-Siestrup Christian , Wendt Constanze , Martiny Heike 
Published: October 2018

ABSTRACT

The survival of three bacterial species and
Candida albicans
was studied on SPI-ARGENT II. The immediate recovery from silver-impregnated polymer and control polymer (1 cm
2
) was ∼10
6
to 10
7
microorganisms. After incubation (37°C) and neutralization of silver with horse serum (5%), surviving organisms were recovered. The survival of the microorganisms on the polymer was not found to be influenced by the silver implantation.
A Ser315Thr Substitution in KatG Is Predominant in Genetically Heterogeneous Multidrug-Resistant
Mycobacterium tuberculosis
Isolates Originating from the St. Petersburg Area in Russia
Authors: Marttila Harri J. , Soini Hanna , Eerola Erkki , Vyshnevskaya Elena , Vyshnevskiy Boris I. , Otten Tatjana F. , Vasilyef Alexandr V. , Viljanen Matti K. 
Published: October 2018

ABSTRACT

Parts of
katG
and
rpoB
from 27 Russian
Mycobacterium tuberculosis
isolates were sequenced to detect mutations causing resistance to isoniazid (INH) and rifampin (RMP), respectively. All 24 INH-resistant isolates had a mutated
katG
, and 22 of them (91.7%) carried a mutation coding for a Ser315Thr shift. An
rpoB
mutation was noted for each of the 21 RMP-resistant isolates, with Ser531Leu being the most prevalent change encoded. Only two isolates had identical IS
6110
fingerprints.
Activity and Diffusion of LY333328 in Experimental Endocarditis Due to Vancomycin-Resistant
Enterococcus faecalis
Authors: Saleh-Mghir Azzam , Lefort Agnès , Petegnief Yolande , Dautrey Sophie , Vallois Jean-Marie , Le Guludec Dominique , Carbon Claude , Fantin Bruno 
Published: October 2018

ABSTRACT

The activity of LY333328 against
Enterococcus faecalis
JH2-2, which is susceptible to glycopeptides, and against its transconjugants
E. faecalis
BM4281 and BM4316, with VanB and VanA phenotypes, respectively, was investigated. LY333328 was active in vitro against the three strains, for which MICs were 2 μg/ml on agar and 0.25 μg/ml in broth. LY333328 was bactericidal in broth against
E. faecalis
JH2-2 and BM4281 at a concentration of 8 μg/ml and against BM4316 at a concentration of 30 μg/ml. The protein binding of LY333328 to rabbit serum was >99%, and the bactericidal activity of LY333328 in broth was reduced when it was tested in the presence of 90% rabbit serum. Autoradiographic studies performed in rabbits with enterococcal endocarditis showed that
14
[C]LY333328 was distributed heterogeneously throughout cardiac vegetations. In rabbits with aortic endocarditis, a regimen of 20 mg of LY333328 per kg of body weight administered intramuscularly twice a day for 5 days after a loading dose of 40 mg/kg was active against the three strains in vivo (
P
< 0.01), whereas vancomycin was not active against the VanB-type strain and teicoplanin was not active against the VanA-type strain. We conclude that the activity of LY333328 is not significantly modified by acquired resistance to glycopeptides in
E. faecalis
either in vitro or in experimental endocarditis.
Eradication by Ceftriaxone of
Streptococcus pneumoniae
Isolates with Increased Resistance to Penicillin in Cases of Acute Otitis Media
Authors: Gehanno P. , Nguyen L. , Barry B. , Derriennic M. , Pichon F. , Goehrs J. M. , Berche P. 
Published: October 2018

ABSTRACT

This multicenter, noncomparative, nonrandomized study evaluated the clinical efficacy and safety of ceftriaxone for treating acute otitis media in children following clinical failure of oral antibiotic therapy. Middle-ear fluid samples were collected on day 0 and on day 3, 4, or 5 (day 3 to 5) and were used to test whether ceftriaxone therapy can eradicate
Streptococcus pneumoniae
isolates with increased resistance to penicillin (MIC ≥ 1 mg/liter). At the first visit, on day 0, middle-ear fluid was sampled for bacteriological testing by tympanocentesis or otorrhea pus suction. Patients were administered 50 mg of ceftriaxone/kg of body weight/day, injected intramuscularly once daily, for 3 days. A second sample was collected by tympanocentesis if a pneumococcus isolate for which the MIC of penicillin was ≥1 mg/liter was detected in the day-0 sample and if the middle-ear effusion persisted on day 3 to 5. This second sample was tested for bacterial eradication. One hundred eighty-six children aged 5 months to 5 years, 10 months, with acute otitis media clinical failure were enrolled and treated in this trial. On day 10 to 12, 145 (83.8%) of the 173 patients evaluable for clinical efficacy were clinically cured. Of the 59 patients infected by pneumococci, 36 had isolates for which the MICs of penicillin were ≥1 mg/liter. Of those patients, on day 10 to 12, 32 (88.9%) were clinically cured. Middle-ear fluid samples collected by day 3 to 5 following the onset of treatment with ceftriaxone were sterile for 24 of the 27 (88.9%) patients who were infected as of day 0 by pneumococci for which the MICs of penicillin were ≥1 mg/liter and who were evaluable for bacteriological eradication. On day 10 to 12, 81.4% of
S. pneumoniae
-infected children and 87.5% of
Haemophilus influenzae
-infected children were clinically cured. No discontinuation of treatment due to adverse events, particularly due to local reactions at the injection site, were reported. Only 11 adverse events which had doubtful, probable, or possible links with the study treatment were recorded. Both the bacteriologically assessed eradication of pneumococci for which the MICs of penicillin were ≥1 mg/liter and the clinical cure rates demonstrate that ceftriaxone is of value in the management of acute otitis media unresponsive to previous oral antibiotic therapy.
Pharmacokinetics in Serum and Leukocyte Exposures of Oral Azithromycin, 1,500 Milligrams, Given over a 3- or 5-Day Period in Healthy Subjects
Authors: Amsden Guy W. , Nafziger Anne N. , Foulds George 
Published: October 2018

ABSTRACTThe pharmacokinetics in serum and leukocyte (WBC) exposures of 1,500 mg of oral azithromycin administered as 3-day (500 mg/day, days 1 to 3) and 5-day (500 mg on day 1 and 250 mg/day on days 2 to 5) regimens were compared in 12 healthy volunteers. Serum, polymorphonuclear leukocytes, and mononuclear leukocytes were collected over a 12-day period from the start of each regimen. Results of the study indicate that the exposures of serum and both types of WBCs were similar with both regimens. Drug concentrations in day 12 WBCs were well above the MICs for all relevant community-acquired respiratory tract pathogens. Terminal half-lives in serum obtained by both regimens were essentially equal at 66 h and consistent with past reports. These results indicate that the standard 1,500-mg dose of oral azithromycin can be administered over either 5 or 3 days.
Identification of an Efflux Pump Gene,
pmrA
, Associated with Fluoroquinolone Resistance in
Streptococcus pneumoniae
Authors: Gill Martin J. , Brenwald Nigel P. , Wise Richard 
Published: October 2018

ABSTRACT

An open reading frame (ORF) homologous to
norA
was insertionally inactivated with
cat
in a fluoroquinolone-resistant pneumococcus with an efflux phenotype; this inactivation caused reversion to drug sensitivity. The ORF product has 24% amino acid sequence identity each to NorA and Bmr, which suggests that it is a major facilitator system pump of the 12-transmembrane-segment class.
Metabolic Studies on BMS-200475, a New Antiviral Compound Active against Hepatitis B Virus
Authors: Yamanaka Gregory , Wilson Todd , Innaimo Steven , Bisacchi Gregory S. , Egli Peter , Rinehart J. Kent , Zahler Robert , Colonno Richard J. 
Published: October 2018

ABSTRACT

BMS-200475 was recently shown to have potent antiviral activity against hepatitis B virus (50% effective concentration = 3.7 nM; 50% cytotoxic concentration = 30 μM). In metabolic studies in both HepG2 and hepatitis B virus-transfected 2.2.15 human hepatoma cell lines, the metabolism was similar, the primary products being the di- and triphosphates. The accumulation of triphosphate was rapid and detectable down to a 5 nM concentration of added drug. When cells were labeled at 25 μM, the intracellular triphosphate concentration attained 30 pmol/10
6
cells (∼30 μM). The intracellular half-life of the triphosphate was about 15 h. Compared with five other nucleoside analogs of medical interest (lamivudine, penciclovir, ganciclovir, acyclovir, and lobucavir), BMS-200475 was most efficiently phosphorylated to the triphosphate in HepG2 cells.
Close Association between Clearance of Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSF) and G-CSF Receptor on Neutrophils in Cancer Patients
Authors: Terashi Kenji , Oka Mikio , Ohdo Shigehiro , Furukubo Taku , Ikeda Chizuko , Fukuda Minoru , Soda Hiroshi , Higuchi Shun , Kohno Shigeru 
Published: October 2018

ABSTRACT

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988–991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 μg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 ± 132 versus 995 ± 266 ml/h;
P
< 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% ± 22.1%) and high at neutrophilia with rhG-CSF therapy (73.0% ± 11.4%;
P
< 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (
r
2
= 0.91;
P
< 0.0001) and neutrophil count (
r
2
= 0.72;
P
< 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.
Evaluation of a Novel, Anti-Herpes Simplex Virus Compound, Acyclovir Elaidate (P-4010), in the Female Guinea Pig Model of Genital Herpes
Authors: Jennings R. , Smith T. L. , Myhren F. , Phillips J. , Sandvold M. L. 
Published: October 2018

ABSTRACTThe antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2′-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.
Low Plasma Cefepime Levels in Critically Ill Septic Patients: Pharmacokinetic Modeling Indicates Improved Troughs with Revised Dosing
Authors: Lipman J. , Wallis S. C. , Rickard C. 
Published: October 2018

ABSTRACT

The pharmacokinetics of a 2-g bolus of cefepime were measured in critically ill patients with normal renal function. Variable and low trough plasma drug concentrations were found, and 8 of 10 patients had levels below the MIC at which 50% of the isolates are inhibited for
Pseudomonas aeruginosa
. Computer simulations predicted that continuous infusion and shorter dosing intervals would increase trough levels.