bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetracycline Resistance in
Salmonella enterica
subsp.
enterica
Serovar Dublin
Authors: Frech Gabriele , Schwarz Stefan 
Published: October 2018

ABSTRACT

The 47-kbp plasmid pGFT1 from
Salmonella enterica
subsp.
enterica
serovar Dublin mediated tetracycline resistance via a
tet
(A) gene located on an integrated copy of a Tn
1721
-analogous transposon. The integration site of the transposon was located within the reading frame of a
fip
gene. Plasmid pGFT1 was shown to be conjugative and to be able to replicate and express tetracycline resistance in
Escherichia coli.
S-1153 Inhibits Replication of Known Drug-Resistant Strains of Human Immunodeficiency Virus Type 1
Authors: Fujiwara Tamio , Sato Akihiko , El-Farrash Mohamed , Miki Shigeru , Abe Kenji , Isaka Yoshitaka , Kodama Makoto , Wu Yaming , Chen Lan Bo , Harada Hiroshi , Sugimoto Hirohiko , Hatanaka Masakazu , Hinuma Yorio 
Published: October 2018

ABSTRACT
S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two- to three-drug combination therapy for HIV infection.
Pharmacokinetics of Sparfloxacin in the Serum and Vitreous Humor of Rabbits: Physicochemical Properties That Regulate Penetration of Quinolone Antimicrobials
Authors: Liu Weiguo , Liu Qing Feng , Perkins Ruth , Drusano George , Louie Arnold , Madu Assumpta , Mian Umar , Mayers Martin , Miller Michael H. 
Published: October 2018

ABSTRACT

We have used a recently described animal model to characterize the ocular pharmacokinetics of sparfloxacin in vitreous humor of uninfected albino rabbits following systemic administration and direct intraocular injection. The relationships of lipophilicity, protein binding, and molecular weight to the penetration and elimination of sparfloxacin were compared to those of ciprofloxacin, fleroxacin, and ofloxacin. To determine whether elimination was active, elimination rates following direct injection with and without probenecid or heat-killed bacteria were compared. Sparfloxacin concentrations were measured in the serum and vitreous humor by a biological assay. Protein binding and lipophilicity were determined, respectively, by ultrafiltration and oil-water partitioning. Pharmacokinetic parameters were characterized with RSTRIP, an iterative, nonlinear, weighted, least-squares-regression program. The relationship between each independent variable and mean quinolone concentration or elimination rate in the vitreous humor was determined by multiple linear regression. The mean concentration of sparfloxacin in the vitreous humor was 59.4% ± 12.2% of that in serum. Penetration of sparfloxacin, ciprofloxacin, fleroxacin, and ofloxacin into, and elimination from, the vitreous humor correlated with lipophilicity (
r
2
> 0.999). The linear-regression equation describing this relationship was not improved by including the inverse of the square root of the molecular weight and/or the degree of protein binding. Elimination rates for each quinolone were decreased by the intraocular administration of probenecid. Heat-killed
Staphylococcus epidermidis
decreased the rate of elimination of fleroxacin. Penetration of sparfloxacin into the noninflamed vitreous humor was greater than that of any quinolone previously examined. There was an excellent correlation between lipophilicity and vitreous entry or elimination for sparfloxacin as well as ciprofloxacin, fleroxacin, and ofloxacin. There are two modes of quinolone translocation into and out of the vitreous humor: diffusion into the eye and both diffusion and carrier-mediated elimination out of the vitreous humor.
Different Erythromycin Resistance Mechanisms in Group C and Group G Streptococci
Authors: Kataja Janne , Seppälä Helena , Skurnik Mikael , Sarkkinen Hannu , Huovinen Pentti 
Published: October 2018

ABSTRACT

Different mechanisms of erythromycin resistance predominate in group C and G streptococcus (GCS and GGS, respectively) isolates collected from 1992 to 1995 in Finland. Of the 21 erythromycin-resistant GCS and 32 erythromycin-resistant GGS isolates, 95% had the
mefA
or
mefE
drug efflux gene and 94% had the
ermTR
methylase gene, respectively.
Mode of Action of Sulfanilyl Fluoroquinolones
Authors: Alovero Fabiana , Nieto Marcelo , Mazzieri Maria Rosa , Then Rudolf , Manzo Ruben H. 
Published: October 2018

ABSTRACT

The mode of action of sulfanilyl fluoroquinolones (NSFQs) was investigated with NSFQ-104, NSFQ-105, and some structurally related compounds. Evidence arising from interactions with
p
-aminobenzoic acid and trimethoprim suggested that a sulfonamidelike mechanism of action makes little or no contribution to the in vitro activity of NSFQs. NSFQ-105 showed an activity that inhibits gyrase-catalyzed DNA supercoiling that is similar to the activity of other fluoroquinolones. Also, NSFQ-105 uptake was decreased by the presence of Mg
2+
and increased by a lower pH. These results indicate that NSFQs having only one ionizable group could exhibit more favorable kinetics of access to the bacterial cell than zwitterionic fluoroquinolones.
Susceptibilities of
Legionella
spp. to Newer Antimicrobials In Vitro
Authors: Schülin T. , Wennersten C. B. , Ferraro M. J. , Moellering R. C. , Eliopoulos G. M. 
Published: October 2018

ABSTRACT

The in vitro activities of 13 antimicrobial agents against 30 strains of
Legionella
spp. were determined. Rifapentine, rifampin, and clarithromycin were the most potent agents (MICs at which 90% of isolates are inhibited [MIC
90
s], ≤0.008 μg/ml). The ketolide HMR 3647 and the fluoroquinolones levofloxacin and BAY 12-8039 (MIC
90
s, 0.03 to 0.06 μg/ml) were more active than erythromycin A or roxithromycin. The MIC
90
s of dalfopristin-quinupristin and linezolid were 0.5 and 8 μg/ml, respectively. Based on class characteristics and in vitro activities, several of these agents may have potential roles in the treatment of
Legionella
infections.
Entry of Sanfetrinem into Human Polymorphonuclear Granulocytes and Its Cell-Associated Activity against Intracellular, Penicillin-Resistant
Streptococcus pneumoniae
Authors: Cuffini Anna Maria , Tullio Vivian , Bonino Alessandro , Allocco Alessandra , Palarchio Angela Ianni , Carlone Nicola A. 
Published: October 2018

ABSTRACT

The entry of antibiotics into phagocytes is necessary for activity against intracellular pathogens. The ability of sanfetrinem, the first member of a new class of antibiotics, to penetrate human polymorphonuclear granulocytes and its consequences upon subsequent phagocytosis and killing of ingested penicillin-resistant
Streptococcus pneumoniae
have been evaluated. Sanfetrinem penetrated into human polymorphonuclear leukocytes (PMNs) at all concentrations tested, with cellular concentration/extracellular concentration ratios of 6.6 to 5.03 and 4.21 when sanfetrinem was used at 0.25 to 0.5 and 1 μg/ml, respectively, within 30 min of incubation. The uptake was complete within 5 min and was not energy dependent, since it was not affected by cell viability, environmental temperature, or the addition of a metabolic inhibitor. At a concentration of one-half the MIC, sanfetrinem significantly enhanced human PMN phagocytosis and increased intracellular bactericidal activity against penicillin-resistant
S. pneumoniae
. Following preexposure of PMNs to a concentration of one-half the MIC of sanfetrinem, there was a significant increase in both phagocytosis and killing compared with that for the controls, indicating the ability of sanfetrinem to interact with biological membranes and remain active within PMNs. Preexposure of streptococci to sanfetrinem made penicillin-resistant
S. pneumoniae
more susceptible to the bactericidal mechanisms of human PMNs than untreated organisms.
Ciprofloxacin Induces an Immunomodulatory Stress Response in Human T Lymphocytes
Authors: Riesbeck Kristian , Forsgren Arne , Henriksson Agnethe , Bredberg Anders 
Published: October 2018

ABSTRACTExposure of cells to adverse environmental conditions invokes a genetically programmed series of events resulting in the induction of specific genes. The fluoroquinolone antibiotic ciprofloxacin has recently been reported to upregulate interleukin-2 (IL-2) gene induction. In the present investigation, the effect of ciprofloxacin at supratherapeutic concentrations on immediate-early (<2 h) gene expression in primary human peripheral blood lymphocytes was studied with Northern blots. In addition, transcriptional activity of IL-2 and metallothionein enhancer and promoter regions and transcription factors AP-1, NF-κB, and NF-AT were analyzed by chloramphenicol acetyltransferase (CAT) and electrophoretic mobility shift assays, respectively. The concentration of c-fos, c-jun, c-myc,junB, andfra-1 mRNAs was increased in activated peripheral blood lymphocytes incubated with ciprofloxacin compared to that in untreated controls. Ciprofloxacin increased CAT activity in stimulated lymphocytes transfected with plasmids containing either the IL-2 or metallothionein enhancer. Furthermore, among the transcription factors tested, AP-1 activity was increased in stimulated purified T helper lymphocytes incubated with ciprofloxacin compared to drug-free controls. Taken together, ciprofloxacin increased the levels of immediate-early transcripts, enhanced IL-2 and metallothionein promoter induction, and upregulated AP-1 concentrations in primary lymphocytes, reflecting a program commonly observed in mammalian stress responses.
vanA
Gene Cluster in a Vancomycin-Resistant Clinical Isolate of
Bacillus circulans
Authors: Ligozzi Marco , Lo Cascio Giuliana , Fontana Roberta 
Published: October 2018

ABSTRACT

We report on the cloning and sequencing of the
vanA
gene cluster present in the glycopeptide-resistant clinical isolate
Bacillus circulans
VR0709 (R. Fontana, M. Ligozzi, C. Pedrotti, E. M. Padovani, and G. Cornaglia, Eur. J. Clin. Microbiol. Infect. Dis. 16:473–474, 1997). The presence of a
vanA
-related gene in VR0709 was demonstrated in a PCR assay which permitted the specific amplification of an internal segment of
vanA
. Southern blotting suggested that the
vanA
gene was located in the chromosome in a 7.6-kb
Eco
RI fragment. DNA sequence analysis revealed the presence of all seven genes of the
vanA
cluster (
vanR
,
vanS
,
vanH
,
vanA
,
vanX
,
vanY
, and
vanZ
). The degree of identity between homologous proteins encoded by Tn
1546
and the chromosome of
B. circulans
VR0709 ranged from 87 to 95%. Neither PCR nor Southern blotting with specific primers and probes, respectively, showed the presence of open reading frames (ORFs) 1 and 2 which encode the transposase and the resolvase of Tn
1546
, respectively, the transposon found to carry the
vanA
gene cluster in enterococci. Determination of the sequences of the flanking regions of the
van
gene cluster of
B. circulans
revealed perfect inverted repeats of 10 bp which delineated a 9.2-kb region containing the
van
gene cluster and an ORF which encoded a putative protein (178 residues) which displayed a low level of identity (28%) to the resolvase of Tn
1546
. These results suggest that glycopeptide resistance in
B. circulans
VR0709 is associated with the acquisition of a
vanA
gene cluster which shows a high degree of homology with that of enterococci. In
B. circulans
, however, the cluster is not carried by Tn
1546
and is borne by the chromosome.
Detection of Tn
917
-Like Sequences within a Tn
916
-like Conjugative Transposon (Tn
3872
) in Erythromycin-Resistant Isolates of
Streptococcus pneumoniae
Authors: McDougal Linda K. , Tenover Fred C. , Lee Linda N. , Rasheed J. Kamile , Patterson Jan E. , Jorgensen James H. , LeBlanc Donald J. 
Published: October 2018

ABSTRACT

A series of macrolide-lincosamide-streptogramin B (MLS)-resistant pneumococcal isolates of a variety of serotypes was examined and was found to contain Tn
917
-like elements by DNA-DNA hybridization. Like Tn
1545
, Tn
917
also encodes an
ermAM
gene but does not mediate resistance to other antimicrobial agents. Furthermore, nucleotide sequence analyses of the DNAs flanking three of the Tn
917
-like elements revealed that they were inserted into
orf9
of a Tn
916
-like element in a composite transposon-like structure (Tn
3872
). Other MLS-resistant strains appeared to contain Tn
1545
-like elements that had suffered a deletion of sequences including the
aphA-3
sequences responsible for kanamycin resistance. Thus, the MLS resistance phenotype in pneumococci appears to be mediated by the
ermAM
present on a much wider variety of genetic elements than was previously appreciated.
Moxifloxacin (BAY12-8039), a New 8-Methoxyquinolone, Is Active in a Mouse Model of Tuberculosis
Authors: Miyazaki Eishi , Miyazaki Miki , Chen Jong Min , Chaisson Richard E. , Bishai William R. 
Published: October 2018

ABSTRACTMoxifloxacin (BAY12-8039) is a new 8-methoxyquinolone shown to be active againstMycobacterium tuberculosisin vitro. We tested moxifloxacin for activity in mice againstM. tuberculosisCSU93, a highly virulent, recently isolated clinical strain. The MIC of moxifloxacin for the CSU93 strain was 0.25 μg/ml. The serum moxifloxacin concentration after oral administration in mice peaked within 0.25 h, reaching 7.8 μg/ml with doses of 100 mg/kg of body weight; the maximum concentration and the analysis of the area under the concentration-time curve revealed dose dependency. When mice were infected with a sublethal inoculum of mycobacteria and then treated with moxifloxacin at 100 mg/kg per day for 8 weeks, the log10CFU counts in the organs of treated mice were significantly lower than those for the control group (0.6 ± 0.2 versus 5.6 ± 0.3 in the lungs and 1.5 ± 0.7 versus 4.9 ± 0.5 in the spleens, respectively;P< 0.001 in both organs). The effectiveness of moxifloxacin monotherapy was comparable to that seen in mice receiving isoniazid alone. Combination therapy with moxifloxacin plus isoniazid was superior to that with moxifloxacin or with isoniazid alone in reducing bacillary counts in the organs studied. Using a sensitive broth-passage subculture method, we demonstrated that 8 weeks of treatment with moxifloxacin (100 mg/kg per day) or with moxifloxacin plus isoniazid (100 mg/kg and 25 mg/kg, respectively, per day) sterilized the lungs in seven of eight and in eight of eight mice, respectively. Among surviving bacilli isolated from animals infected with a high-titer inoculum and treated for 7 weeks with low-dose moxifloxacin (20 mg/kg per day), breakthrough resistance to moxifloxacin was not observed. These results indicate that moxifloxacin is highly effective in reducingM. tuberculosisinfection in mice and has activity comparable to that of isoniazid. Combination therapy with moxifloxacin and isoniazid was highly effective, suggesting that moxifloxacin may be useful in multiple-drug regimens for human tuberculosis.
Penetration of Moxifloxacin into Peripheral Compartments in Humans
Authors: Müller Markus , Staß Heino , Brunner Martin , Möller Jan G. , Lackner Edith , Eichler Hans G. 
Published: October 2018

ABSTRACT

To characterize the penetration of moxifloxacin (BAY 12-8039) into peripheral target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, an innovative clinical sampling technique. In addition, moxifloxacin concentrations were measured in cantharides-induced skin blisters, saliva, and capillary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in an open randomized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min. An almost-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed, with mean area under the concentration-time curve (AUC)
interstitial fluid
/AUC
total-plasma
ratios ranging from 0.38 to 0.55 and mean AUC
interstitial fluid
/AUC
free-plasma
ratios ranging from 0.81 to 0.86. The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h, indicating a preferential penetration of moxifloxacin into inflamed lesions. The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels in plasma. Our data show that moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90% of isolates are inhibited for most clinically relevant bacterial strains, notably including penicillin-resistant
Streptococcus pneumoniae
. These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans.
Inhibition of Human Immunodeficiency Virus Type 1 Replication in Acutely and Chronically Infected Cells by EM2487, a Novel Substance Produced by aStreptomycesSpecies
Authors: Baba Masanori , Okamoto Mika , Takeuchi Hitoshi 
Published: October 2018

ABSTRACTIn a search for effective HIV-1 transcription inhibitors, we have evaluated more than 75,000 compounds for their inhibitory effects on Tat-induced human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-driven reporter gene expression and found that EM2487, a novel small-molecule substance produced by aStreptomycesspecies, is a potent and selective inhibitor of HIV-1 replication in both acutely and chronically infected cells. Its 50% effective concentration for acute HIV-1 infection was 0.27 μM in peripheral blood mononuclear cells (PBMCs), while the 50% cytotoxic concentration for mock-infected PBMCs was 13.3 μM. EM2487 proved inhibitory to a variety of HIV-1 strains and HIV-2 in acutely infected T-cell lines (MOLT-4 and MT-4). The compound could suppress tumor necrosis factor alpha (TNF-α)-induced HIV-1 production in latently infected cells (OM-10.1 and ACH-2) as well as constitutive viral production in chronically infected cells (MOLT-4/IIIBand U937/IIIB) without showing any cytotoxicity. EM2487 did not affect early events of the HIV-1 replication cycle, as determined by proviral DNA synthesis in acutely infected MOLT-4 cells. In contrast, the compound selectively prevented viral mRNA synthesis in OM-10.1 cells, suggesting that HIV-1 inhibition occurs at the transcriptional level. Furthermore, EM2487 did not inhibit TNF-α-induced HIV-1 LTR-driven reporter gene expression but did inhibit that induced by Tat, irrespective of the presence or absence of the nuclear factor κB binding sites in the LTR. These results suggest that the mechanism of action is attributable in part to the inhibition of Tat function.
β-Lactamase Production in
Prevotella intermedia
,
Prevotella nigrescens
, and
Prevotella pallens
Genotypes and In Vitro Susceptibilities to Selected Antimicrobial Agents
Authors: Mättö Jaana , Asikainen Sirkka , Väisänen Marja-Liisa , Von Troil-Lindén Birgitta , Könönen Eija , Saarela Maria , Salminen Kari , Finegold Sydney M. , Jousimies-Somer Hannele 
Published: October 2018

ABSTRACT

The present study investigated the β-lactamase production of 73
Prevotella intermedia
, 84
Prevotella nigrescens
, and 14
Prevotella pallens
isolates and their in vitro susceptibilities to six antimicrobial agents. The
P. intermedia
and
P. nigrescens
isolates were recovered from oral and extraoral samples obtained from subjects in two geographic locations from 1985 to 1995. The clonality of the β-lactamase-positive and β-lactamase-negative isolates and the clustering of the genotypes were studied by arbitrarily primed-PCR fingerprinting. β-Lactamase production was detected in 29% of
P. intermedia
isolates, 29% of
P. nigrescens
isolates, and 57% of
P. pallens
isolates. No difference in the frequencies of β-lactamase production by
P. intermedia
and
P. nigrescens
between isolates from oral and extraoral sites, between isolates obtained at different time periods, or between
P. intermedia
isolates from different geographic locations was observed. However, the
P. nigrescens
isolates from the United States were significantly more frequently (
P
= 0.015) β-lactamase positive than those from Finland. No association between the genotypes and β-lactamase production or between the genotypes and the sources of the isolates was found. The penicillin G MICs at which 90% of the isolates were inhibited were 8 μg/ml for
P. intermedia
, 8 μg/ml for
P. nigrescens
, and 16 μg/ml for
P. pallens
. For the β-lactamase-negative isolates, the corresponding values were 0.031, 0.031, and 0.125 μg/ml, and for the β-lactamase-positive isolates, the corresponding values were 16, 8, and 32 μg/ml. All isolates were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, azithromycin, and trovafloxacin. The MICs of amoxicillin-clavulanate and cefoxitin were relatively higher for the β-lactamase-positive population than for the β-lactamase-negative population.
Reconstruction of an Active Integron Recombination Site after Integration of a Gene Cassette at a Secondary Site
Authors: Segal Heidi , Francia M. Victoria , Lobo Juan M. García , Elisha Gay 
Published: October 2018

ABSTRACT

As the site of insertion of the
aadB
gene cassette on pRAY, from a clinical isolate of
Acinetobacter
, is almost identical to the preferred site on integrons, the composite 59-base element (59-BE) associated with this cassette is potentially recombinationally active. By using a conduction assay to quantitate site activity, the 59-BE was recognized by integrase with high frequency, indicating that the composite site is recombinationally active.
Synergy Testing of Vancomycin-Resistant
Enterococcus faecium
against Quinupristin-Dalfopristin in Combination with Other Antimicrobial Agents
Authors: Matsumura S. O. , Louie L. , Louie M. , Simor A. E. 
Published: October 2018

ABSTRACT

Using checkerboard and time-kill assays, we evaluated the in vitro activity of quinupristin-dalfopristin (RP 59500) alone and in combination with five other antimicrobial agents against 12 clinical strains of vancomycin-resistant
Enterococcus faecium
(VREF). In time-kill studies, six VREF strains exhibited synergism with the combination of quinupristin-dalfopristin and doxycycline and three exhibited synergism with quinupristin-dalfopristin plus ampicillin-sulbactam. Combinations of quinupristin-dalfopristin with these and other agents warrant further clinical evaluation for the treatment of serious VREF infections.
Mutations in 23S rRNA in
Helicobacter pylori
Conferring Resistance to Erythromycin Do Not Always Confer Resistance to Clarithromycin
Authors: García-Arata M. Isabel , Baquero Fernando , de Rafael Luis , de Argila Carlos Martín , Gisbert Javier P. , Bermejo Fernando , Boixeda Daniel , Cantón Rafael 
Published: October 2018

ABSTRACT

Mutations conferring resistance to erythromycin or clarithromycin in
Helicobacter pylori
were studied. Mutation A2142G was consistently associated with clarithromycin MIC of >256 μg/ml, whereas mutants carrying A2143G had MICs ranging from ≤0.016 to >256 μg/ml, suggesting that additional factors account for the observed multiple levels of resistance to clarithromycin.