bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Levofloxacin for Experimental Aortic-Valve Endocarditis in Rabbits Infected with Viridans Group Streptococcus orStaphylococcus aureus
Authors: Chambers Henry F. , Xiang Qing , Liu  , Chow Lucian Liuxin , Hackbarth Corinne 
Published: October 2018

ABSTRACTLevofloxacin is among the more active fluoroquinolones against streptococci and staphylococci. It is effective against moderately severe infections caused by these organisms, but its efficacy in the treatment of bacteremia and serious infections such as endocarditis is not well defined. We compared the efficacy of levofloxacin to those of standard agents in the rabbit model of aortic-valve endocarditis caused by fluoroquinolone-susceptible strains including a penicillin-susceptible strain ofStreptococcus sanguis, a penicillin-resistant strain ofStreptococcus mitis, a methicillin-resistant strain ofStaphylococcus aureus, and a methicillin-susceptible strain ofS. aureus. Levofloxacin administered intramuscularly at dosages of 20 to 40 mg/kg of body weight twice daily (b.i.d.) was completely ineffective against the penicillin-susceptible strain, with mean vegetation titers after 3 days of therapy not statistically significantly different from those for controls. Levofloxacin was no more effective than penicillin against the penicillin-resistant strain. Levofloxacin administered for 4 days at a dosage of 20 mg/kg b.i.d. was at least as effective as vancomycin administered intravenously at a dosage of 25 mg/kg b.i.d. against the methicillin-resistantS. aureusstrain and was as effective as nafcillin administered intramuscularly at 100 mg three times daily against the methicillin-susceptible strain. Emergence of resistance to levofloxacin in vitro was less likely to occur than resistance to ciprofloxacin, and resistance to levofloxacin was not observed in vivo. Levofloxacin-rifampin combinations were antagonistic in vitro and in vivo. Levofloxacin was highly effective as a single agent against experimental staphylococcal endocarditis but was surprisingly ineffective against streptococcal endocarditis, suggesting that it has a potential role as treatment for seriousS. aureusbut not viridans group streptococcal infections in humans.
In Vitro Activities of Gemifloxacin (SB 265805, LB20304) against Recent Clinical Isolates of
Chlamydia pneumoniae
Authors: Roblin Patricia M. , Reznik Tamara , Kutlin Andrei , Hammerschlag Margaret R. 
Published: October 2018

ABSTRACT

We compared the in vitro activity of gemifloxacin, a new quinolone antibiotic, to the activities of levofloxacin, moxifloxacin, trovafloxacin, erythromycin, and doxycycline against 20 isolates of
Chlamydia pneumoniae
. Gemifloxacin was the most active quinolone tested, with a MIC at which 90% of the isolates are inhibited and a minimal bactericidal concentration at which 90% of strains tested are killed of 0.25 μg/ml, but this activity was less than those of doxycycline and erythromycin.
Interaction between Fluconazole and Amphotericin B in Mice with Systemic Infection Due to Fluconazole-Susceptible or -Resistant Strains of
Candida albicans
Authors: Louie Arnold , Banerjee Partha , Drusano George L. , Shayegani Mehdi , Miller Michael H. 
Published: October 2018

ABSTRACT

The interaction between fluconazole (Flu) and amphotericin B (AmB) was evaluated in a murine model of systemic candidiasis for one Flu-susceptible strain (MIC, 0.5 μg/ml), two strains with intermediate Flu resistance (Flu mid-resistant strains) (MIC, 64 and 128 μg/ml), and one highly Flu-resistant strain (MIC, 512 μg/ml) of
Candida albicans
. Differences in fungal densities in kidneys of infected mice after 24 h of therapy and in survival rates at 62 days of mice treated with an antifungal drug or a combination of antifungal drugs for 4 days were compared. For the Flu-susceptible and Flu mid-resistant strains, the combination of Flu and AmB was antagonistic, as shown by both quantitative culture results and survival. The interaction was additive for the highly Flu-resistant strain. These results suggest that the combination of Flu and AmB should be used with caution in infections due to fungi that are usually susceptible to both antifungal agents and as empirical antifungal drug therapy.
Automated Thermal Cycling Is Superior to Traditional Methods for Nucleotide Sequencing of
bla
SHV
Genes
Authors: Bradford Patricia A. 
Published: October 2018

ABSTRACT
Genes encoding SHV-1 and SHV-2 were sequenced by different methods. Nucleotide sequencing of the coding strand by standard dideoxy-chain termination methods resulted in errors in the interpretation of the nucleotide sequence and the derived amino acid sequence in two main regions which corresponded to nucleotide and amino acid changes that had been reported previously. The automated thermal cycling method was clearly superior and consistently resulted in the correct sequences for these genes.
Gatifloxacin Activity against Quinolone-Resistant Gyrase: Allele-Specific Enhancement of Bacteriostatic and Bactericidal Activities by the C-8-Methoxy Group
Authors: Lu Tao , Zhao Xilin , Drlica Karl 
Published: October 2018

ABSTRACT

Antibacterial activities of gatifloxacin (AM1155), a new C-8-methoxy fluoroquinolone, and two structurally related compounds, AM1121 and ciprofloxacin, were studied with an isogenic set of ten quinolone-resistant,
gyrA
(gyrase) mutants of
Escherichia coli
. To compare the effect of each mutation on resistance, the mutant responses were normalized to those of wild-type cells. Alleles exhibiting the most resistance to growth inhibition mapped in α-helix 4, which is thought to lie on a GyrA dimer surface that interacts with DNA. The C-8-methoxy group lowered the resistance due to these mutations more than it lowered resistance arising from several
gyrA
alleles located outside α-helix 4. These data are consistent with α-helix 4 being a distinct portion of the quinolone-binding site of GyrA. A helix change to proline behaved more like nonhelix alleles, indicating that helix perturbation differs from the other changes at helix residues. Addition of a
parC
(topoisomerase IV) resistance allele revealed that the C-8-methoxy group also facilitated attack of topoisomerase IV. When lethal effects were measured at a constant multiple of the minimum inhibitory concentration for each fluoroquinolone to normalize for differences in bacteriostatic action, gatifloxacin was more potent than the C-8-H compounds, both in the presence and absence of protein synthesis (an exception was observed when alanine was substituted for aspartic acid at position 82). Collectively, these data show that the C-8-methoxy group contributes to the enhanced activity of gatifloxacin against resistant gyrase and wild-type topoisomerase IV.
Characterization of a
Pseudomonas aeruginosa
Efflux Pump Contributing to Aminoglycoside Impermeability
Authors: Westbrock-Wadman Shannon , Sherman David R. , Hickey Mark J. , Coulter Silvija N. , Zhu Ya Qi , Warrener Paul , Nguyen Lisa Y. , Shawar Ribhi M. , Folger Kim R. , Stover C. Kendall 
Published: October 2018

ABSTRACT

Pseudomonas aeruginosa
can employ many distinct mechanisms of resistance to aminoglycoside antibiotics; however, in cystic fibrosis patients, more than 90% of aminoglycoside-resistant
P. aeruginosa
isolates are of the impermeability phenotype. The precise molecular mechanisms that produce aminoglycoside impermeability-type resistance are yet to be elucidated. A subtractive hybridization technique was used to reveal gene expression differences between PAO1 and isogenic, spontaneous aminoglycoside-resistant mutants of the impermeability phenotype. Among the many genes found to be up-regulated in these laboratory mutants were the
amrAB
genes encoding a recently discovered efflux system. The
amrAB
genes appear to be the same as the recently described
mexXY
genes; however, the resistance profile that we see in
P. aeruginosa
is very different from that described for
Escherichia coli
with
mexXY
. Direct evidence for AmrAB involvement in aminoglycoside resistance was provided by the deletion of
amrB
in the PAO1-derived laboratory mutant, which resulted in the restoration of aminoglycoside sensitivity to a level nearly identical to that of the parent strain. Furthermore, transcription of the
amrAB
genes was shown to be up-regulated in
P. aeruginosa
clinical isolates displaying the impermeability phenotype compared to a genotypically matched sensitive clinical isolate from the same patient. This suggests the possibility that AmrAB-mediated efflux is a clinically relevant mechanism of aminoglycoside resistance. Although it is unlikely that hyperexpression of AmrAB is the sole mechanism conferring the impermeability phenotype, we believe that the Amr efflux system can contribute to a complex interaction of molecular events resulting in the aminoglycoside impermeability-type resistance phenotype.
Antibiotic-Induced Cell Wall Fragments ofStaphylococcus aureusIncrease Endothelial Chemokine Secretion and Adhesiveness for Granulocytes
Authors: van Langevelde P. , Ravensbergen E. , Grashoff P. , Beekhuizen H. , Groeneveld P. H. P. , van Dissel J. T. 
Published: October 2018

ABSTRACTAntibiotics release inflammatory fragments, such as lipoteichoic acid (LTA) and peptidoglycan (PG), from the cell wall ofStaphylococcus aureus. In this study, we exposedS. aureuscultures to a number of β-lactam antibiotics (imipenem, flucloxacillin, and cefamandole) and protein synthesis-inhibiting antibiotics (erythromycin, clindamycin, and gentamicin) and investigated whether supernatants of these cultures differ in their capacity to stimulate endothelial cells (EC). After 24 h of incubation, endothelial adhesiveness for leukocytes, surface expression of various adhesion molecules, and secretion of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were measured. Supernatants of β-lactam-exposed cultures (designated β-lactam supernatants) enhanced the adhesiveness of EC for granulocytes, whereas those of protein synthesis-inhibiting antibiotic-exposed cultures (designated protein synthesis-inhibitor supernatants) did not. This hyperadhesiveness coincided with a higher intercellular adhesion molecule-1 expression on the surface of the stimulated EC. In addition, EC stimulated with β-lactam supernatants secreted significantly higher concentrations of the chemokines IL-8 and MCP-1 than those stimulated with protein synthesis-inhibitor supernatants. The finding that the concentrations of LTA and PG in β-lactam supernatants were much higher than those in protein synthesis-inhibitor supernatants suggests that the observed differences in stimulatory effect between these supernatants are a result of differences in the release of cell wall fragments, although the presence of other stimulatory factors in the supernatants cannot be excluded. In conclusion, our results argue for a release of LTA and PG fromS. aureusafter exposure to β-lactam antibiotics that enhances the development of a systemic inflammatory response by stimulating EC such that adhesiveness for granulocytes is increased and large amounts of IL-8 and MCP-1 are secreted.
Antimicrobial Resistance of Diarrheagenic
Escherichia coli
Isolated from Children under the Age of 5 Years from Ifakara, Tanzania
Authors: Vila Jordi , Vargas Martha , Casals Climent , Urassa Honorato , Mshinda Hassan , Schellemberg David , Gascon Joaquim 
Published: October 2018

ABSTRACT

Diarrhea caused by multidrug-resistant bacteria is an important public health problem among children in developing countries. The prevalence and antimicrobial susceptibility of diarrheagenic
Escherichia coli
in 346 children under 5 years of age in Ifakara, Tanzania, were studied. Thirty-eight percent of the cases of diarrhea were due to multiresistant enterotoxigenic
E. coli
, enteroaggregative
E. coli
, or enteropathogenic
E. coli
. Strains of all three
E. coli
categories showed high-level resistance to ampicillin, tetracycline, co-trimoxazole, and chloramphenicol but were highly susceptible to quinolones. Guidelines for appropriate use of antibiotics in developing countries need updating.
A Broad-Spectrum Microbicide with Virucidal Activity against Sexually Transmitted Viruses
Authors: Howett M. K. , Neely E. B. , Christensen N. D. , Wigdahl B. , Krebs F. C. , Malamud D. , Patrick S. D. , Pickel M. D. , Welsh P. A. , Reed C. A. , Ward M. G. , Budgeon L. R. , Kreider J. W. 
Published: October 2018

ABSTRACTSodium dodecyl sulfate (SDS), an alkyl sulfate surfactant derived from an organic alcohol, possesses surfactant properties but also denatures and unfolds both monomeric and subunit proteins. In preliminary experiments, we demonstrated that SDS is a potent inactivator of herpes simplex virus type 2 and human immunodeficiency virus type 1 at concentrations comparable to those used for the surfactant nonoxynol-9. We hypothesized that SDS might be capable of denaturing the capsid proteins of nonenveloped viruses. In this report, we demonstrate inactivation of rabbit, bovine, and human papillomaviruses after brief treatment with dilute solutions of SDS. Effective concentrations were nontoxic to rabbit skin and to split-thickness grafts of human foreskin epithelium. This is the first report of a microbicidal surfactant that will inactivate papillomaviruses. We propose that SDS is now a candidate microbicide for formulation and testing with humans.
Pharmacokinetics of Mefloquine Combined with Artesunate in Children with Acute Falciparum Malaria
Authors: Price Ric , Simpson Julie A. , Teja-Isavatharm Paktiya , Than Myint Myint , Luxemburger Christine , Gray Heppner D. , Chongsuphajaisiddhi Tan , Nosten François , White Nicholas J. 
Published: October 2018

ABSTRACT
Combining artemisinin or a derivative with mefloquine increases cure rates in falciparum malaria patients, reduces transmission, and may slow the development of resistance. The combination of artesunate, given for 3 days, and mefloquine is now the treatment of choice for uncomplicated multidrug-resistant falciparum malaria acquired on the western or eastern borders of Thailand. To optimize mefloquine administration in this combination, a prospective study of mefloquine pharmacokinetics was conducted with 120 children (4 to 15 years old) with acute uncomplicated falciparum malaria, who were divided into four age- and sex-matched groups. The patients all received artesunate (4 mg/kg of body weight/day orally for 3 days and mefloquine as either (i) a single dose (25 mg/kg) on day 2 with food, (ii) a split dose (15 mg/kg on day 2 and 10 mg/kg on day 3) with food, (iii) a single dose (25 mg/kg) on day 0 without food, or (iv) a single dose (25 mg/kg) on day 2 without food. Delaying administration of mefloquine until day 2 was associated with a mean (95% confidence interval) increase in estimated oral bioavailability of 72% (36 to 109%). On day 2 coadministration with food did not increase mefloquine absorption significantly, and there were no significant differences between patients receiving split- and single-dose administration. In combination with artesunate, mefloquine administration should be delayed until the second or third day after presentation.
Antisense Oligonucleotide Inhibition of Hepatitis C Virus (HCV) Gene Expression in Livers of Mice Infected with an HCV-Vaccinia Virus Recombinant
Authors: Zhang Hong , Hanecak Ronnie , Brown-Driver Vickie , Azad Raana , Conklin Boyd , Fox Maureen C. , Anderson Kevin P. 
Published: October 2018

ABSTRACT
Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Current treatments are not curative for most infected individuals, and there is an urgent need for both novel therapeutic agents and small-animal models which can be used to evaluate candidate drugs. A small-animal model of HCV gene expression was developed with recombinant vaccinia virus vectors. VHCV-IRES (internal ribosome entry site) is a recombinant vaccinia viral vector containing the HCV 5′ nontranslated region (5′-NTR) and a portion of the HCV core coding region fused to the firefly luciferase gene. Intraperitoneal injection of VHCV-IRES produced high levels of luciferase activity in the livers of BALB/c mice. Antisense oligonucleotides complementary to the HCV 5′-NTR and translation initiation codon regions were then evaluated for their effects on the expression of these target HCV sequences in BALB/c mice infected with the vaccinia virus vector. Treatment of VHCV-IRES-infected mice with 20-base phosphorothioate oligonucleotides complementary to the sequence surrounding the HCV initiation codon (nucleotides 330 to 349) specifically reduced luciferase expression in the livers in a dose-dependent manner. Inhibition of HCV reporter gene expression in this small-animal model suggests that antisense oligonucleotides may provide a novel therapy for treatment of chronic HCV infection.
Primary Targets of Fluoroquinolones in
Streptococcus pneumoniae
Authors: Fukuda Hideyuki , Hiramatsu Keiichi 
Published: October 2018

ABSTRACT

Mutants of wild-type
Streptococcus pneumoniae
IID553 with mutations in
parC
were obtained by selection with trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin. All of the
parC
mutants were cross-resistant to the selecting agents but were not resistant to gatifloxacin and sparfloxacin. On the other hand,
gyrA
mutants were isolated by selection with gatifloxacin and sparfloxacin. The
gyrA
mutants were cross-resistant to gatifloxacin and sparfloxacin but were not resistant to the other fluoroquinolones tested. These results suggest that in wild-type
S. pneumoniae
the primary target of trovafloxacin, levofloxacin, norfloxacin, and ciprofloxacin is topoisomerase IV, whereas the primary target of gatifloxacin and sparfloxacin is DNA gyrase.
Italian Survey on Comparative Levofloxacin Susceptibility in 334 Clinical Isolates of
Pseudomonas aeruginosa
Authors: Segatore Bernardetta , Setacci Domenico , Perilli Mariagrazia , Franceschini Nicola , De Santis Annalisa , Marchetti Federico , Amicosante Gianfranco 
Published: October 2018

ABSTRACT

A national survey on susceptibility patterns of 334
Pseudomonas aeruginosa
isolates from intensive care units and hematology and oncology wards from 13 Italian hospitals compared the in vitro activity of levofloxacin, an injectable oral fluoroquinolone, to those of ciprofloxacin, ofloxacin, ceftazidime, imipenem, amikacin, and gentamicin. Amikacin and imipenem had the best susceptibility profiles. The activity of levofloxacin was superior to those of the other quinolones and was comparable to that of ceftazidime. The effect of levofloxacin in vitro on
P. aeruginosa
clinical isolates suggests that further clinical investigations are warranted.
Molecular Diversity and Evolutionary Relationships of Tn
1546
-Like Elements in Enterococci from Humans and Animals
Authors: Willems Rob J. L. , Top Janetta , van den Braak Nicole , van Belkum Alex , Mevius Dik J. , Hendriks Giel , van Santen-Verheuvel Marga , van Embden Jan D. A. 
Published: October 2018

ABSTRACT

We report on a detailed study on the molecular diversity and evolutionary relationships of Tn
1546
-like elements in vancomycin-resistant enterococci (VRE) from humans and animals. Restriction fragment length polymorphism (RFLP) analysis of the VanA transposon of 97 VRE revealed seven different Tn
1546
types. Subsequent sequencing of the complete VanA transposons of 13 VRE isolates representing the seven RFLP types followed by sequencing of the identified polymorphic regions in 84 other VanA transposons resulted in the identification of 22 different Tn
1546
derivatives. Differences between the Tn
1546
types included point mutations in
orf1
,
vanS
,
vanA
,
vanX
, and
vanY
. Moreover, insertions of an IS
1216V
-IS
3
-like element in
orf1
, of IS
1251
in the
vanS-vanH
intergenic region, and of IS
1216V
in the
vanX-vanY
intergenic region were found. The presence of insertion sequence elements was often associated with deletions in Tn
1546
. Identical Tn
1546
types were found among isolates from humans and farm animals in The Netherlands, suggesting the sharing of a common vancomycin resistance gene pool. Application of the genetic analysis of Tn
1546
to VRE isolates causing infections in hospitals in Oxford, United Kingdom, and Chicago, Ill., suggested the possibility of the horizontal transmission of the vancomycin resistance transposon. The genetic diversity in Tn
1546
combined with epidemiological data suggest that the DNA polymorphism among Tn
1546
variants can successfully be exploited for the tracing of the routes of transmission of vancomycin resistance genes.
Pharmacokinetics and Urinary Excretion of Amikacin in Low-Clearance Unilamellar Liposomes after a Single or Repeated Intravenous Administration in the Rhesus Monkey
Authors: Fielding Robert M. , Moon-Mcdermott Lotus , Lewis Ramilla O. , Horner Michelle J. 
Published: October 2018

ABSTRACT

Liposomal aminoglycosides have been shown to have activity against intracellular infections, such as those caused by
Mycobacterium avium
. Amikacin in small, low-clearance liposomes (MiKasome) also has curative and prophylactic efficacies against
Pseudomonas aeruginosa
and
Klebsiella pneumoniae
. To develop appropriate dosing regimens for low-clearance liposomal amikacin, we studied the pharmacokinetics of liposomal amikacin in plasma, the level of exposure of plasma to free amikacin, and urinary excretion of amikacin after the administration of single-dose (20 mg/kg of body weight) and repeated-dose (20 mg/kg eight times at 48-h intervals) regimens in rhesus monkeys. The clearance of liposomal amikacin (single-dose regimen, 0.023 ± 0.003 ml min
−1
kg
−1
; repeated-dose regimen, 0.014 ± 0.001 ml min
−1
kg
−1
) was over 100-fold lower than the creatinine clearance (an estimate of conventional amikacin clearance). Half-lives in plasma were longer than those reported for other amikacin formulations and declined during the elimination phase following administration of the last dose (from 81.7 ± 27 to 30.5 ± 5 h). Peak and trough (48 h) levels after repeated dosing reached 728 ± 72 and 418 ± 60 μg/ml, respectively. The levels in plasma remained >180 μg/ml for 6 days after the administration of the last dose. The free amikacin concentration in plasma never exceeded 17.4 ± 1 μg/ml and fell rapidly (half-life, 1.47 to 1.85 h) after the administration of each dose of liposomal amikacin. This and the low volume of distribution (45 ml/kg) indicate that the amikacin in plasma largely remained sequestered in long-circulating liposomes. Less than half the amikacin was recovered in the urine, suggesting that the level of renal exposure to filtered free amikacin was reduced, possibly as a result of intracellular uptake or the metabolism of liposomal amikacin. Thus, low-clearance liposomal amikacin could be administered at prolonged (2- to 7-day) intervals to achieve high levels of exposure to liposomal amikacin with minimal exposure to free amikacin.
Treatment of Murine Fusariosis with SCH 56592
Authors: Lozano-Chiu M. , Arikan S. , Paetznick V. L. , Anaissie E. J. , Loebenberg D. , Rex J. H. 
Published: October 2018

ABSTRACT

Doses of 10 to 100 mg of the azole antifungal agent SCH 56592/kg of body weight/day were studied in immunocompetent mice as therapy for systemic infection by
Fusarium solani
. Treatment was begun 1 h after intravenous infection and continued daily for 4 or 13 doses. Prolongation of survival and organ clearance were dependent on both the dose and the duration of SCH 56592 therapy, with the best results seen at 50 and 100 mg/kg/day. The results at the highest doses of SCH 56592 used (50 or 100 mg/kg/day) were comparable to those obtained with amphotericin B at 1 mg/kg/day. SCH 56592 has potential for therapy of systemic infections caused by
F. solani
.