bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilocus Genotypes and DNA Fingerprints Do Not Predict Variation in Azole Resistance among Clinical Isolates of
Candida albicans
Authors: Cowen Leah E. , Sirjusingh Caroline , Summerbell Richard C. , Walmsley Sharon , Richardson Susan , Kohn Linda M. , Anderson James B. 
Published: October 2018

ABSTRACT

If variation in azole resistance is due to inherent differences in strains of
Candida albicans
, as a predominantly clonal organism, then correlation between multilocus genotypes and drug resistance would be expected. A sample of 81 clinical isolates from patients infected with human immunodeficiency virus in Toronto, Canada, plus 3 reference isolates were genotyped at 16 loci, distributed on all linkage groups, by means of oligonucleotide hybridizations specific for each of the alleles at each locus. These multilocus genotypes were significantly correlated with DNA fingerprints obtained with the species-specific probe 27A, indicating widespread linkage disequilibrium in the genome. There were 64 multilocus diploid genotypes and 77 DNA fingerprint types delineated in this sample. Neither the multilocus genotyping nor DNA fingerprinting alone identified all of the 81 types identified by the combination of these two methods. Multilocus genotypes were not predictive of fluconazole resistance, suggesting that resistance is gained or lost too quickly to be predicted by linkage with neutral markers.
The
pfmdr1
Gene Is Associated with a Multidrug-Resistant Phenotype in
Plasmodium falciparum
from the Western Border of Thailand
Authors: Price R. N. , Cassar C. , Brockman A. , Duraisingh M. , van Vugt M. , White N. J. , Nosten F. , Krishna S. 
Published: October 2018

ABSTRACT

On the western border of Thailand,
Plasmodium falciparum
has become resistant to almost all antimalarial agents. The molecular basis of resistance in these parasite populations has not been well characterized. This study assessed genetic polymorphisms in the
pfmdr1
gene in 54 parasites collected from the western border of Thailand to determine the relationship of
pfmdr1
copy number and codon mutations with parasite sensitivities to mefloquine, chloroquine, halofantrine, quinine, and artesunate assessed in vitro. A point mutation at codon 86 (resulting in a change of Asn to Tyr) was associated with a significantly lower 50% inhibitory concentration (IC
50
) of mefloquine (median, 9 ng/ml versus 52.4 ng/ml;
P
= 0.003). Overall 35% of the isolates (19 of 54) had an increase in
pfmdr1
copy number, and all 19 carried the wild-type allele at codon 86. Increased
pfmdr1
copy number was associated with higher IC
50
s of mefloquine (
P
= 0.04) and artesunate (
P
= 0.005), independent of polymorphism at codon 86. The relationship between
pfmdr1
and resistance to structurally distinct antimalarial agents confirms the presence of a true multidrug-resistant phenotype.
Determination of Zidovudine Triphosphate Intracellular Concentrations in Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Individuals by Tandem Mass Spectrometry
Authors: Font Eva , Rosario Osvaldo , Santana Jorge , García Hermes , Sommadossi Jean-Pierre , Rodriguez Jose F. 
Published: October 2018

ABSTRACT

Nucleoside reverse transcriptase inhibitors (NRTIs) used against the human immunodeficiency virus (HIV) need to be activated intracellularly to their triphosphate moiety to inhibit HIV replication. Intracellular concentrations of these NRTI triphosphates, especially zidovudine triphosphate (ZDV-TP), are relatively low (low numbers of femtomoles per 10
6
cells) in HIV-infected patient peripheral blood mononuclear cells. Recently, several methods have used either high-performance liquid chromatography (HPLC) or solid-phase extraction (SPE) coupled with radioimmunoassay to obtain in vivo measurements of ZDV-TP. The limit of detection (LOD) by these methods ranged from 20 to 200 fmol/10
6
cells. In this report, we describe the development of a method to determine intracellular ZDV-TP concentrations in HIV-infected patients using SPE and HPLC with tandem mass spectrometry for analysis. The LOD by this method is 4.0 fmol/10
6
cells with a linear concentration range of at least 4 orders of magnitude from 4.0 to 10,000 fmol/10
6
cells. In hispanic HIV-infected patients, ZDV-TP was detectable even when the sampling time after drug administration was 15 h. Intracellular ZDV-TP concentrations in these patients ranged from 41 to 193 fmol/10
6
cells. The low LOD obtained with this method will provide the opportunity for further in vivo pharmacokinetic studies of intracellular ZDV-TP in different HIV-infected populations. Furthermore, this methodology could be used to perform simultaneous detection of two or more NRTIs, such as ZDV-TP and lamivudine triphosphate.
Activity of Gemifloxacin against Penicillin- and Ciprofloxacin-Resistant
Streptococcus pneumoniae
Displaying Topoisomerase- and Efflux-Mediated Resistance Mechanisms
Authors: Heaton Victoria J. , Goldsmith Colin E. , Ambler Jane E. , Fisher L. Mark 
Published: October 2018

ABSTRACT

Nine penicillin-resistant
Streptococcus pneumoniae
clinical isolates from Northern Ireland, resistant to ciprofloxacin (MICs, 2 to 64 μg/ml) through topoisomerase- and/or reserpine-sensitive efflux mechanisms, were highly susceptible to gemifloxacin (MICs, 0.03 to 0.12 μg/ml). Two strains (requiring a ciprofloxacin MIC of 64 μg/ml) carried known quinolone resistance mutations in
parC
,
parE
, and
gyrB
, resulting in S79F, D435V, and E474K changes, respectively. Thus, gemifloxacin is active against clinical strains exhibiting altered topoisomerase and efflux phenotypes.
Comparative In Vitro Antimicrobial Activities of the Newly Synthesized Quinolone HSR-903, Sitafloxacin (DU-6859a), Gatifloxacin (AM-1155), and Levofloxacin against
Mycobacterium tuberculosis
and
Mycobacterium avium
Complex
Authors: Tomioka Haruaki , Sato Katsumasa , Akaki Tatsuya , Kajitani Hiroko , Kawahara Shin , Sakatani Mitsunori 
Published: October 2018

ABSTRACT

We compared the in vitro antimycobacterial activity of a new fluoroquinolone, HSR-903, with strong activity against gram-positive cocci with those of levofloxacin (LVFX), sitafloxacin (STFX), and gatifloxacin (GFLX). The MICs of the quinolones for
Mycobacterium tuberculosis
and
Mycobacterium avium
complex were in the order STFX ≈ GFLX < LVFX ≦ HSR-903 and STFX ≦ GFLX ≦ HSR-903 ≦ LVFX, respectively. HSR-903 effectively eliminated intramacrophagial
M. tuberculosis
, as did LVFX, and exhibited bacteriostatic effects against
M. tuberculosis
replicating in type II alveolar cells.
High-Level Aminoglycoside Resistance in the Beta-Hemolytic Group G
Streptococcus
Isolate BM2721
Authors: Galimand Marc , Lambert Thierry , Gerbaud Guy , Courvalin Patrice 
Published: October 2018

ABSTRACT

The beta-hemolytic group G
Streptococcus
clinical isolate BM2721 was resistant to high levels of aminoglycosides by synthesis of AAC(6′)-APH(2"), APH(3′)-III, and ANT(6) modifying enzymes. The corresponding genes were found to be adjacent as the result of a recombination event between Tn
4001
and Tn
5405
, two transposons originating in staphylococci.
Distribution of β-Lactamases in Actinomycetes
Authors: Ogawara Hiroshi , Kawamura Nao , Kudo Takuji , Suzuki Ken-Ichiro , Nakase Takashi 
Published: October 2018

ABSTRACT

The distribution of β-lactamase activities in a collection of actinomycete strains was surveyed. Six of 127 strains were found to produce β-lactamase. This low frequency was in contrast to the case with
Streptomyces
species. The producing strains were not related phylogenetically. MICs of benzylpenicillin did not correlate with β-lactamase production.
Genetic Characterization of Antimicrobial Resistance in Canadian Isolates of
Salmonella
Serovar Typhimurium DT104
Authors: Ng Lai-King , Mulvey Michael R. , Martin Irene , Peters Geoffrey A. , Johnson Wendy 
Published: October 2018

ABSTRACT

PCR was used to identify antibiotic resistance determinants in 31 Canadian
Salmonella
serovar Typhimurium DT104 isolates. Genes encoding resistance to ampicillin (
pse1
or
blaP1
), chloramphenicol (
pasppflo
-like), streptomycin-spectinomycin (
aadA2
), sulfonamide (
sulI
), and tetracycline [
tet
(G)] were mapped to a 13-kb region of DNA of one isolate. Two copies of
sulI
were identified and mapped to the 3′ end of either
pse1
or
aadA2
integrons. The two integrons were separated by the
pasppflo
-like gene and the
tet
(G) gene. The kanamycin resistance determinant (
aphA-1
) was present on a 2.0-MDa plasmid (five isolates) or on the chromosome (three isolates).
Comparative In Vitro Activities of Meropenem, Imipenem, Temocillin, Piperacillin, and Ceftazidime in Combination with Tobramycin, Rifampin, or Ciprofloxacin against
Burkholderia cepacia
Isolates from Patients with Cystic Fibrosis
Authors: Bonacorsi Stephane , Fitoussi Frederic , Lhopital Sylvie , Bingen Edouard 
Published: October 2018

ABSTRACT

We evaluated the activities of meropenem, imipenem, temocillin, piperacillin, and ceftazidime by determination of the MICs for 66 genotypically characterized
Burkholderia cepacia
isolates obtained from the sputum of cystic fibrosis patients. In vitro synergy assays, as performed by the time-kill methodology, of two- and three-drug combinations of the β-lactams with tobramycin, rifampin, and/or ciprofloxacin were also performed with 10 strains susceptible, intermediate, or resistant to fluoroquinolones. On the basis of the MICs, meropenem and temocillin were the most active β-lactam agents, with MICs at which 90% of isolates are inhibited of 8 and 32 μg/ml, respectively. The addition of ciprofloxacin significantly enhanced the killing activities of piperacillin, imipenem, and meropenem against the 10 strains tested (
P
< 0.05). The best killing activity was obtained with the combination of meropenem and ciprofloxacin, with bactericidal activity of 3.31 ± 0.36 log
10
CFU/ml (
P
< 0.05). Compared to the activity of the two-drug β-lactam–ciprofloxacin combination, the addition of rifampin or tobramycin did not significantly increase the killing activity (
P
> 0.05). The three-drug combinations (with or without ciprofloxacin) significantly enhanced the killing activities of piperacillin, imipenem, and meropenem relative to the activities of the β-lactams used alone (
P
< 0.05). The combination β-lactam–ciprofloxacin–tobramycin was the combination with the most consistently synergistic effect.
Amphotericin B and Fluconazole Affect Cellular Charge, Macrophage Phagocytosis, and Cellular Morphology ofCryptococcus neoformansat Subinhibitory Concentrations
Authors: Nosanchuk Joshua D. , Cleare Wendy , Franzot Sarah P. , Casadevall Arturo 
Published: October 2018

ABSTRACTAmphotericin B (AmB) and fluconazole (FLU) are the major antifungal drugs used in the treatment of cryptococcosis. Both drugs are believed to exert their antifungal effects through actions on cell membrane sterols. In this study we investigated whether AmB and FLU had other, more subtle effects onC. neoformansthat could contribute to their therapeutic efficacy.C. neoformanscells were grown in media with subinhibitory concentrations of either AmB or FLU and analyzed for cellular charge, phagocytosis by macrophages with antibody and complement opsonins, appearance by scanning electron and light microscopies, and release of the capsular polysaccharide glucuronoxylomannan into the culture medium. Growth in the presence of either AmB or FLU resulted in major reductions in cellular charge, as measured by determination of the zeta potential. Phagocytosis studies demonstrated that exposure ofC. neoformansto subinhibitory concentrations of AmB or FLU enhanced phagocytosis by macrophages. Scanning electron microscopy revealed that a large proportion of cells had an altered capsular appearance. Cells grown in medium with either AmB or FLU were smaller and released more glucuronoxylomannan into the culture medium than cells grown without antibiotics. The results suggest additional mechanisms of action for AmB and FLU that may be operative in body compartments where drug levels do not achieve the MICs. Furthermore, the results suggest mechanisms by which AmB and FLU can cooperate with humoral and cellular immune defense systems in controllingC. neoformansinfections.
glmM
Operon and Methicillin-Resistant
glmM
Suppressor Mutants in
Staphylococcus aureus
Authors: Glanzmann Philipp , Gustafson John , Komatsuzawa Hithoshi , Ohta Kouji , Berger-Bächi Brigitte 
Published: October 2018

ABSTRACT

The
Staphylococcus aureus
phosphoglucosamine mutase gene
glmM
was shown to be the last gene of a three-cistron operon,
orf1-orf2-glmM
. One transcriptional start was identified upstream of
orf1
, and a second start producing a monocistronic transcript was identified upstream of
glmM
. Disruption of
glmM
abolished GlmM production, decreased methicillin resistance, and resulted in teicoplanin hypersusceptibility without affecting the production of the endogenous penicillin-binding proteins and PBP 2′. Complementation of the
glmM
mutation by the complete
glmM
operon restored both methicillin resistance and normal teicoplanin susceptibility. In contrast, a highly methicillin-resistant suppressor mutant obtained by selection for growth in the presence of methicillin remained GlmM deficient and teicoplanin hypersusceptible. The suppressor mutation was not linked to the
glmM
operon but was correlated with decreased autolysis and increased production of a 49-kDa protein, suggesting that there is an alternative pathway for glucosamine-1-phosphate synthesis in
S. aureus.
Comparison of a New Triazole Antifungal Agent, Schering 56592, with Itraconazole and Amphotericin B for Treatment of Histoplasmosis in Immunocompetent Mice
Authors: Connolly Patricia , Wheat Joe , Schnizlein-Bick Carol , Durkin Michelle , Kohler Steve , Smedema Melinda , Goldberg Janet , Brizendine Edward , Loebenberg David 
Published: October 2018

ABSTRACTA murine model of intratracheally induced histoplasmosis was used to evaluate a new triazole antifungal agent, Schering (SCH) 56592, for treatment of histoplasmosis. MICs were determined for SCH 56592, amphotericin B, and itraconazole by testing yeast-phase isolates from 20 patients by a macrobroth dilution method. The MICs at which 90% of the isolates are inhibited were for 0.019 μg/ml for SCH 56592, 0.5 μg/ml for amphotericin B, and ≤0.019 μg/ml for itraconazole. Survival studies were done on groups of 10 B6C3F1mice with a lethal inoculum of 105. All mice receiving 5, 1, or 0.25 mg of SCH 56592 per kg of body weight per day, 2.5 mg of amphotericin B per kg every other day (qod), or 75 mg of itraconazole per kg per day survived to day 29. Only 44% of mice receiving 5 mg of itraconazole/kg/day survived to day 29. Fungal burden studies done in similar groups of mice with a sublethal inoculum of 104showed a reduction in CFUs andHistoplasmaantigen levels in lung and spleen tissue in animals treated with 2 mg of amphotericin B/kg qod, 1 mg of SCH 56592/kg/day, and 75 mg of itraconazole/kg/day, but not in those treated with lower doses of the study drugs (0.2 mg of amphotericin B/kg qod, 0.1 mg of SCH 56592/kg/day, or 10 mg of itraconazole/kg/day). Serum drug concentrations were measured 3 and 24 h after the last dose in mice (groups of five to seven mice), each treated for 7 days with SCH 56592 (10 and 1 mg/kg/day) and itraconazole (75 and 10 mg/kg/day). Mean levels measured by bioassay were as follows: SCH 56592, 10 mg/kg/day (2.15 μg/ml at 3 h and 0.35 μg/ml at 24 h); SCH 56592, 1 mg/kg/day (0.54 μg/ml at 3 h and none detected at 24 h); itraconazole, 75 mg/kg/day (22.53 μg/ml at 3 h and none detected at 24 h); itraconazole, 10 mg/kg/day (1.33 μg/ml at 3 h and none detected at 24 h). Confirmatory results were obtained by high-pressure liquid chromatography assay. These studies show SCH 56592 to be a promising candidate for studies of treatment of histoplasmosis in humans.
Enterococci with Acquired Vancomycin Resistance in Pigs and Chickens of Different Age Groups
Authors: Butaye Patrick , Devriese Luc A. , Goossens Herman , Ieven Margaretha , Haesebrouck Freddy 
Published: October 2018

ABSTRACT
Results for isolation of glycopeptide-resistant enterococci from fecal samples of pigs and chickens were found to differ strongly depending upon the type and age of animals and isolation technique (direct selective plate or broth enrichment). Isolations were frequent in broiler chickens and in sows but rare in layer chickens.
Fungal Lethality, Binding, and Cytotoxicity of Syringomycin-E
Authors: De Lucca A. J. , Jacks T. J. , Takemoto J. , Vinyard B. , Peter J. , Navarro E. , Walsh T. J. 
Published: October 2018

ABSTRACT

Syringomycin-E (SE) was significantly lethal to
Aspergillus
and
Fusarium
species at between 1.9 and 7.8 μg/ml. SE complexed with the following fungal wall constituents (in order of binding): β-1,3-glucan > chitin > mannan > ergosterol = cholesterol. Cytotoxicity in HeLa cells was proportional to the SE concentration, while the amount required for cytotoxicity was 3 to 20 times that needed to kill 95% of the fungi tested.
Resistance of
Pseudomonas aeruginosa
to Imipenem Induced by Eluates from Siliconized Latex Urinary Catheters Is Related to Outer Membrane Protein Alterations
Authors: Martínez-Martínez Luis , Pascual Alvaro , del Carmen Conejo María , Picabea Leandro , Perea Evelio J. 
Published: October 2018

ABSTRACT

The activity of imipenem against
Pseudomonas aeruginosa
HUS-3 decreased by 16 times in the presence of substances eluted from siliconized latex urinary catheters (SLUCs). SLUCs did not inactivate imipenem or increase β-lactamase activity. The outer membrane of
P. aeruginosa
HUS-3 grown in the presence of eluate lacked an OprD-like protein and expressed a new 50-kDa protein. The decreased activity of imipenem against
P. aeruginosa
in the presence of SLUCs is related to the loss of an OprD-like protein and the expression of a new outer membrane protein.
Mycobacteriocidal Action of Exogenous Nitric Oxide
Authors: Long Richard , Light Bruce , Talbot James A. 
Published: October 2018

ABSTRACTWe tested the hypothesis that exposure of extracellularMycobacterium tuberculosisto low concentrations (<100 ppm) of nitric oxide (NO) for short periods (24 h or less) will result in microbial killing. We observed that NO had both dose- and time-dependent cidal effects that were very significant by two-way analysis of variance (Fratios of 13.4 [P< 0.001] and 98.1 [P< 0.0001], respectively). Conceivably, extracellular bacilli in patients with pulmonary tuberculosis might be vulnerable to exogenous NO.
Detection of
gyrA
Mutations among 335
Pseudomonas aeruginosa
Strains Isolated in Japan and Their Susceptibilities to Fluoroquinolones
Authors: Takenouchi Takashi , Sakagawa Eiko , Sugawara Mie 
Published: October 2018

ABSTRACT

gyrA
point mutations in 335 clinical
Pseudomonas aeruginosa
isolates were examined mainly by nonisotopic single-strand conformation polymorphism analysis and direct sequencing. Seven types of missense
gyrA
mutations were observed in 70 of 335 strains (20.9%), and ciprofloxacin MICs were ≥3.13 μg/ml for 63 of 70 strains (90.0%). These included two double point mutations and three novel mutations (Ala-67→Ser plus Asp-87→Gly, Ala-84→Pro, and Gln-106→Leu). Thr-83→Ile mutants were predominantly observed (63 of 70 mutants) and showed high-level fluoroquinolone resistance (ciprofloxacin MIC at which 50% of isolates are inhibited, 25 μg/ml).
An Alternative Animal Model for Comparison of Treatments for Cryptococcal Meningitis
Authors: Najvar Laura K. , Bocanegra Rosie , Graybill John R. 
Published: October 2018

ABSTRACT

Weanling outbred rats were infected with
Cryptococcus neoformans
by direct percranial puncture and inoculation into the cranium. A lethal infection ensued. Treatment with LY295337, a depsipeptide with antifungal activity, was effective in prolonging survival and reducing fungal counts in brain tissue. Weanling rats are an acceptable model for the study of central nervous system infection with
C. neoformans
.
In Vitro Activities of Aminomethyl-Substituted Analogs of Novel Tetrahydrofuranyl Carbapenems
Authors: Weiss William J. , Petersen Peter J. , Jacobus Nilda V. , Lin Yang-I , Bitha Panayota , Testa Raymond T. 
Published: October 2018

ABSTRACT

CL 188,624, CL 190,294, and CL 191,121 are novel aminomethyl tetrahydrofuranyl (THF)-1β-methylcarbapenems. The in vitro antibacterial activities of these THF carbapenems were evaluated and compared with those of biapenem, imipenem, and meropenem against 554 recent clinical isolates obtained from geographically distinct medical centers across North America. The antibacterial activities of the THF carbapenems were equivalent to that of biapenem, and the THF carbapenems were slightly more active than imipenem and less active than meropenem against most of the members of the family
Enterobacteriaceae
but lacked significant activity against
Pseudomonas
isolates. In general, CL 191,121 was two- to fourfold more active than CL 188,624 and CL 190,294 against the staphylococcal and enterococcal isolates tested. CL 191,121 was twofold less active than imipenem against methicillin-susceptible staphylococci and was as activity as imipenem against
Enterococcus faecalis
isolates. Biapenem and meropenem were two- and fourfold less active than CL 191,121, respectively, against the methicillin-susceptible staphylococci and
E. faecalis
. All the carbapenems displayed equivalent good activities against the streptococci. Biapenem was slightly more active than the other carbapenems against
Bacteroides fragilis
isolates. Time-kill curve studies demonstrated that the THF carbapenems were bactericidal in 6 h against
Escherichia coli
and
Staphylococcus aureus
isolates. The postantibiotic effect exerted by CL 191,121 was comparable to or slightly longer than that of imipenem against isolates of
S. aureus
,
E. coli
, and
Klebsiella pneumoniae.
Influences of Urinary pH on Ciprofloxacin Pharmacokinetics in Humans and Antimicrobial Activity In Vitro versus Those of Sparfloxacin
Authors: Kamberi Marika , Tsutsumi Kimiko , Kotegawa Tsutomu , Kawano Koichi , Nakamura Koichi , Niki Yoshihito , Nakano Shigeyuki 
Published: October 2018

ABSTRACT

The impact of acidification and alkalinization of urine on the pharmacokinetics of ciprofloxacin was investigated after single 200-mg oral doses were administered to nine healthy male volunteers. In addition, the effect of human urine on the MICs of ciprofloxacin and sparfloxacin against some common urinary tract pathogens such as
Escherichia coli
and
Pseudomonas aeruginosa
was investigated. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride or sodium bicarbonate, respectively. Plasma ciprofloxacin levels in all subjects were adequately described in terms of two-compartment model kinetics with first-order absorption. Acidification and alkalinization treatments had no effect on ciprofloxacin absorption, distribution, or elimination. The total amount of unchanged ciprofloxacin excreted over 24 h under acidic conditions was 88.4 ± 14.5 mg (mean ± standard deviation) (44.2% of the oral dose) and 82.4 ± 16.5 mg (41.2% of the oral dose) under alkaline conditions, while the total amount of unchanged drug excreted over 24 h in volunteers receiving neither sodium bicarbonate nor ammonium chloride was 90.53 ± 9.8 mg (45.2% of the oral dose). The mean renal clearance of ciprofloxacin was 16.78 ± 2.67, 16.08 ± 3.2, and 16.31 ± 2.67 liters/h with acidification, alkalinization, and control, respectively. Renal clearance and concentrations of ciprofloxacin in urine were not correlated with urinary pH. The antibacterial activity of ciprofloxacin and sparfloxacin against
E. coli
NIHJ JC-2 and
P. aeruginosa
ATCC 27853 was affected by human urine and in particular by its pH. The activities of both quinolones against
E. coli
NIHJ JC-2 were lower at lower urinary pH and rather uniform, while in the case of
P. aeruginosa
ATCC 27853 ciprofloxacin was more active than sparfloxacin.