bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Antimicrobial Resistance in Respiratory Tract Isolates of
Streptococcus pneumoniae
: Results of a Canadian National Surveillance Study
Authors: Zhanel George G. , Karlowsky James A. , Palatnick Lorraine , Vercaigne Laverne , Low Donald E. ,   The Canadian Respiratory Infection Study Group, Hoban Daryl J. 
Published: October 2018

ABSTRACT

From October 1997 to November 1998, 1,180 respiratory tract isolates of
Streptococcus pneumoniae
were collected from 18 medical centers in 9 of the 10 Canadian provinces. Penicillin-intermediate and -resistant isolates occurred at rates of 14.8 and 6.4%, respectively, and these rates varied considerably by geographic region. Trimethoprim-sulfamethoxazole, tetracycline, and macrolide rates of nonsusceptibility were 12.2, 10.6, and 8.0 to 9.3%, respectively. The most potent agents studied were newer fluoroquinolones.
Drug Efflux and
parC
Mutations Are Involved in Fluoroquinolone Resistance in Viridans Group Streptococci
Authors: Ferrándiz María José , Oteo Jesús , Aracil Belén , Gómez-Garcés Jose Luis , De La Campa Adela G. 
Published: October 2018

ABSTRACT

Nine ciprofloxacin-resistant viridans group streptococci isolated from asymptomatic carriers were analyzed. Identification to the species level by using three different commercial systems and a PCR-based approach was inconsistent. The nucleotide sequences of fragments of the
parC
,
parE
,
gyrA
, and
gyrB
genes showed considerable intra- and interspecies variations, and these variations mainly involved silent mutations. Three isolates had changes in Ser-79 of ParC (to Phe or Tyr). Phenotypic characterization indicated that eight of the nine isolates had a putative efflux mechanism that would confer low-level resistance to ciprofloxacin.
Treatment of Experimental Staphylococcal Endocarditis Due to a Strain with Reduced Susceptibility In Vitro to Vancomycin: Efficacy of Ampicillin-Sulbactam
Authors: Backo Mirjana , Gaenger Eliza , Burkart Anna , Chai Yin Li , Bayer Arnold S. 
Published: October 2018

ABSTRACT

We evaluated several 3-day antimicrobial regimens in the treatment of experimental endocarditis caused by an oxacillin-resistant
Staphylococcus aureus
strain exhibiting intermediate susceptibility in vitro to vancomycin (VISA). Neither vancomycin alone nor trovafloxacin exhibited in vivo efficacy; addition of amikacin to vancomycin yielded a modest in vivo effect. In contrast, the combination of ampicillin and sulbactam was highly effective in vivo, causing a mean decrease in VISA vegetation densities of >5 log
10
CFU/g versus those of untreated controls.
Antimicrobial Susceptibilities and Serogroups of Clinical Strains of
Clostridium difficile
Isolated in France in 1991 and 1997
Authors: Barbut Frédéric , Decré Dominique , Burghoffer Béatrice , Lesage Danièle , Delisle Françoise , Lalande Valérie , Delmée Michel , Avesani Véronique , Sano Nassita , Coudert Cyril , Petit Jean-Claude 
Published: October 2018

ABSTRACT

Glycopeptides (vancomycin and teicoplanin) and metronidazole are the drugs of choice for the treatment of
Clostridium difficile
infections, but trends in susceptibility patterns have not been assessed in the past few years. The objective was to study the MICs of glycopeptides and metronidazole for unrelated
C. difficile
strains isolated in 1991 (
n
= 100) and in 1997 (
n
= 98) by the agar macrodilution, the E-test, and the disk diffusion methods. Strain susceptibilities to erythromycin, clindamycin, tetracycline, rifampin, and chloramphenicol were also determined by the ATB ANA gallery (bioMérieux, La Balme-les-Grottes, France). The MICs at which 50% of isolates are inhibited (MIC
50
s) and MIC
90
s of glycopeptides and metronidazole remained stable between 1991 and 1997. All the strains were inhibited by concentrations that did not exceed 2 μg/ml for vancomycin and 1 μg/ml for teicoplanin. Comparison of MICs determined by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards and the E test showed correlations (±2 dilutions) of 86.6, 95.9, and 99% for metronidazole, vancomycin, and teicoplanin, respectively. The E test always underestimated the MICs. Strains with decreased susceptibility to metronidazole (MICs, ≥8 μg/ml) were isolated from six patients (
n
= 4 in 1991 and
n
= 2 in 1997). These strains were also detected by the disk diffusion method (zone inhibition diameter, ≤21 mm); they belonged to nontoxigenic serogroup D (
n
= 5) and toxigenic serogroup H (
n
= 1). Decreased susceptibility to erythromycin (MICs, ≥1 μg/ml), clindamycin (MICs, ≥2 μg/ml), tetracycline (MICs, ≥8 μg/ml), rifampin (MICs, ≥4 μg/ml), and chloramphenicol (MICs, ≥16 μg/ml) was observed in 64.2, 80.3, 23.7, 22.7, and 14.6% of strains, respectively. Strains isolated in 1997 were more susceptible than those isolated in 1991, and this trend was correlated to a major change in serogroup distribution. Periodic studies are needed in order to detect changes in serogroups and the emergence of strains with decreased susceptibility to therapeutic drugs.
Kinetics of Antiviral Activity and Intracellular Pharmacokinetics of Human Immunodeficiency Virus Type 1 Protease Inhibitors in Tissue Culture
Authors: Nascimbeni Michelina , Lamotte Claire , Peytavin Gilles , Farinotti Robert , Clavel François 
Published: October 2018

ABSTRACT
We have examined the kinetics of the inhibition of human immunodeficiency virus type 1 (HIV-1) particle infectivity by protease inhibitors (PIs) in cell culture, using either transfected HeLa cells or infected peripheral blood mononuclear cells (PBMCs) as producers of infectious virions. Both the kinetics of the initiation of antiviral activity after addition of the PIs to these cultures and the kinetics of restoration of virion infectivity after removal of the PIs from the treated cultures were examined. We found that the kinetics of initiation of particle infectivity inhibition produced by a high extracellular concentration (5 μM) of the inhibitors were similar for all five inhibitors tested: loss of particle infectivity was perceptible as early as 1 h after the initiation of PI treatment and increased gradually thereafter. By contrast, the durability of this antiviral effect following removal of the drug from the culture varied dramatically according to the drug studied. In transfected HeLa cells, saquinavir and nelfinavir exerted the most prolonged inhibition, with the half-lives of their antiviral activities being greater than 24 h, while ritonavir exerted an intermediate length of inhibition (18 h) and indinavir and amprenavir exerted a reproducibly shorter length of inhibition (5 h). For all five tested PIs, these kinetics were significantly faster in PBMCs than in HeLa cells. The striking differences in antiviral kinetics observed among the different PIs appear mostly due to differences in their intracellular concentrations and/or rates of cellular clearance. Our observations, although limited to tissue culture conditions, may help delineate the cellular parameters of the antiviral activities of HIV-1 PIs and further optimize the efficiencies of these antiretrovirals in vivo.
Diversity of TEM Mutants in
Proteus mirabilis
Authors: Bonnet R. , De Champs C. , Sirot D. , Chanal C. , Labia R. , Sirot J. 
Published: October 2018

ABSTRACT

In a survey of resistance to amoxicillin among clinical isolates of
Proteus mirabilis
, 10 TEM-type β-lactamases were characterized: (i) the well-known penicillinases TEM-1 and TEM-2, the extended-spectrum β-lactamases (ESBLs) TEM-3 and TEM-24, and the inhibitor-resistant TEM (IRT) TEM-44 and (ii) five novel enzymes, a penicillinase TEM-57 similar to TEM-1, an ESBL TEM-66 similar to TEM-3, and three IRTs, TEM-65, TEM-73, and TEM-74. The penicillinase TEM-57 and the ESBL TEM-66 differed from TEM-1 and TEM-3, respectively, by the amino acid substitution Gly-92→Asp (nucleotide mutation G-477→A). This substitution could have accounted for the decrease in pIs (5.2 for TEM-57 and 6.0 for TEM-66) but did not necessarily affect the intrinsic activities of these enzymes. The IRT TEM-65 was an IRT-1-like IRT (Cys-244) related to TEM-2 (Lys-39). The two other IRTs, TEM-73 and TEM-74, were related to IRT-1 (Cys-244) and IRT-2 (Ser-244), respectively, and harbored the amino acid substitutions Leu-21→Phe and Thr-265→Met. In this study, the ESBLs TEM-66, TEM-24, and TEM-3 were encoded by large (170- to 180-kb) conjugative plasmids that exhibited similar patterns after digestion and hybridization with the TEM and AAC(6′)I probes. The three IRTs TEM-65, TEM-73, and TEM-74 were encoded by plasmids that ranged in size from 42 to 70 kb but for which no transfer was obtained. The characterization of five new plasmid-mediated TEM-type β-lactamases and the first report of TEM-24 in
P. mirabilis
are evidence of the wide diversity of β-lactamases produced in this species and of its possible role as a β-lactamase-encoding plasmid reservoir.
Civamide (
cis
-Capsaicin) for Treatment of Primary or Recurrent Experimental Genital Herpes
Authors: Bourne N. , Bernstein D. I. , Stanberry L. R. 
Published: October 2018

ABSTRACT

Neuropharmacologic agents able to disrupt normal virus-neuron interactions may provide an alternative strategy for the treatment of herpes simplex virus (HSV) infections. We have previously shown that prophylactic treatment with capsaicin, a natural compound that alters function in sensory neurons, can protect guinea pigs against cutaneous HSV disease, even though the compound has no direct antiviral activity. Here we have examined the ability of civamide, the
cis
isomer of capsaicin, to interfere with HSV disease. We show that, even when the onset of treatment was delayed until after intravaginal virus challenge, primary genital skin disease severity was significantly reduced. In addition, animals treated during primary infection subsequently experienced a long-lasting reduction in recurrent disease. Civamide treatment during latent infection also significantly reduced recurrent disease, although for a shorter period. Further a single weekly treatment with civamide during latent infection was sufficient to reduce recurrent disease, indicating that an infrequent suppressive maintenance therapy might be possible.
Decreased Antipyrine Clearance following Endotoxin Administration: In Vivo Evidence of the Role of Nitric Oxide
Authors: Kitaichi Kiyoyuki , Wang Li , Takagi Kenji , Iwase Mitsunori , Shibata Eiji , Nadai Masayuki , Takagi Kenzo , Hasegawa Takaaki 
Published: October 2018

ABSTRACT

Klebsiella pneumoniae
endotoxin has been found to decrease hepatic P450-mediated drug-metabolizing enzyme activity in a time-dependent manner. In this study, we investigated the role of nitric oxide (NO) in the decrease in hepatic drug-metabolizing enzyme activity caused by endotoxin in vivo. We measured in vivo pharmacokinetic parameters of antipyrine in rats treated with endotoxin and/or a selective inhibitor of inducible NO synthase (iNOS),
S
-methylisothiourea. Intraperitoneal injection of endotoxin (1 mg/kg of body weight) dramatically decreased the systemic clearance of antipyrine, reflecting reduced hepatic drug-metabolizing enzyme activity, and significantly increased the level of nitrite and nitrate (NOx) in the plasma.
S
-Methylisothiourea (10 mg/kg) reversed this decreasing antipyrine clearance and reduced the level of NOx in plasma. Repeated injections of an NO donor, (±)-(
E
)-4-ethyl-2-[(
E
)-hydroxyimino]-5-nitro-3-hexenamide (FK-409; 10 mg/kg), at a dose which maintained plasma NOx at the same levels as those caused by endotoxin injection, also decreased the systemic clearance of antipyrine. These findings suggest that the overproduction of NO observed in this animal model is at least partially responsible for the significant reduction in the hepatic drug-metabolizing enzyme activity that may happen in a gram-negative bacterial infection.
The ATP Binding Cassette Transporter Gene
CgCDR1
from
Candida glabrata
Is Involved in the Resistance of Clinical Isolates to Azole Antifungal Agents
Authors: Sanglard Dominique , Ischer Françoise , Calabrese David , Majcherczyk Paul A. , Bille Jacques 
Published: October 2018

ABSTRACT

The resistance mechanisms to azole antifungal agents were investigated in this study with two pairs of
Candida glabrata
clinical isolates recovered from two separate AIDS patients. The two pairs each contained a fluconazole-susceptible isolate and a fluconazole-resistant isolate, the latter with cross-resistance to itraconazole and ketoconazole. Since the accumulation of fluconazole and of another unrelated substance, rhodamine 6G, was reduced in the azole-resistant isolates, enhanced drug efflux was considered as a possible resistance mechanism. The expression of multidrug efflux transporter genes was therefore examined in the azole-susceptible and azole-resistant yeast isolates. For this purpose,
C. glabrata
genes conferring resistance to azole antifungals were cloned in a
Saccharomyces cerevisiae
strain in which the ATP binding cassette (ABC) transporter gene
PDR5
was deleted. Three different genes were recovered, and among them, only
C. glabrata CDR1
(
CgCDR1
), a gene similar to the
Candida albicans
ABC transporter
CDR
genes, was upregulated by a factor of 5 to 8 in the azole-resistant isolates. A correlation between upregulation of this gene and azole resistance was thus established. The deletion of
CgCDR1
in an azole-resistant
C. glabrata
clinical isolate rendered the resulting mutant (DSY1041) susceptible to azole derivatives as the azole-susceptible clinical parent, thus providing genetic evidence that a specific mechanism was involved in the azole resistance of a clinical isolate. When
CgCDR1
obtained from an azole-susceptible isolate was reintroduced with the help of a centromeric vector in DSY1041, azole resistance was restored and thus suggested that a
trans
-acting mutation(s) could be made responsible for the increased expression of this ABC transporter gene in the azole-resistant strain. This study demonstrates for the first time the determinant role of an ABC transporter gene in the acquisition of resistance to azole antifungals by
C. glabrata
clinical isolates.
Effects of F171 Mutations in the 6′-
N
-Acetyltransferase Type Ib [AAC(6′)-Ib] Enzyme on Susceptibility to Aminoglycosides
Authors: Chavideh Ramona , Sholly Steven , Panaite Doina , Tolmasky Marcelo E. 
Published: October 2018

ABSTRACT

Substitutions at position F171 of 6′-
N
-acetyltransferase type Ib cause variable loss of aminoglycoside resistance, indicating that this residue plays an important role in the structure and/or function of the enzyme.
Azithromycin as Treatment for Disseminated
Mycobacterium avium
Complex in AIDS Patients
Authors: Koletar Susan L. , Berry Alison J. , Cynamon Michael H. , Jacobson Jeffrey , Currier Judith S. , MacGregor Rob Roy , Dunne Michael W. , Williams Debra J. 
Published: October 2018

ABSTRACT

This multicenter, randomized, dose-ranging study was performed to determine the safety and efficacy of two different doses of azithromycin for treating disseminated
Mycobacterium avium
complex (MAC) in patients with AIDS. Eighty-eight AIDS patients with symptoms and blood cultures consistent with disseminated MAC were treated with 600 or 1,200 mg of azithromycin daily for 6 weeks; 62 patients completed the entire 6 weeks of study. Of note, this study was done prior to the time when combination antiretroviral or anti-MAC regimens were the standard of care. Over the 6-week study period, symptomatic improvement was noted in both dose groups. Microbiological responses were comparable, with mean decreases of 1.5 and 2.0 log CFU/ml in the high- and low-dose groups, respectively. Sterilization of blood cultures occurred in 54% of samples; patients with lower baseline colony counts were more likely to achieve culture negativity. Resistance developed in one patient. Gastrointestinal symptoms were the most common side effects and were more frequent in patients receiving 1,200 mg. Azithromycin is a useful alternative treatment for disseminated MAC infection in AIDS patients. Symptomatic improvement correlates with measurable decreases in mycobacterial load.
Activities of the Oxazolidinones Linezolid and Eperezolid in Experimental Intra-Abdominal Abscess Due to
Enterococcus faecalis
or Vancomycin-Resistant
Enterococcus faecium
Authors: Schülin T. , Thauvin-Eliopoulos C. , Moellering R. C. , Eliopoulos G. M. 
Published: October 2018

ABSTRACT

The in vivo effectiveness of oxazolidinones eperezolid (U-100592) and linezolid (U-100766) against one strain each of
Enterococcus faecalis
and vancomycin-resistant
Enterococcus faecium
was examined in a rat model of intra-abdominal abscess. MICs of both drugs were 2 μg/ml for each strain. At doses of 25 mg/kg of body weight twice daily intravenously or orally, linezolid produced small but statistically significant reductions in abscess bacterial density for
E. faecalis
. The reduction in viable cells observed would not likely be clinically relevant. Eperezolid was ineffective at this dose. At a dosage of 100 mg/kg/day, linezolid treatment led to an approximately 100-fold reduction in viable cells per gram of abscess. Against
E. faecium
infections, intravenous eperezolid and oral linezolid were effective, reducing densities approximately 2 log
10
CFU/g. Both oxazolidinones demonstrated activity against enterococci in this model. However, results were modest with the dosing regimens employed.
Activities of Poloxamer CRL-1072 againstMycobacterium aviumin Macrophage Culture and in Mice
Authors: Jagannath Chinnaswamy , Emanuele Martin R. , Hunter Robert L. 
Published: October 2018

ABSTRACTEarlier studies reported that certain large hydrophobic poloxamer surfactants were able to inhibit the growth ofMycobacterium avium-M. intracellularecomplex (MAI) in broth and to produce synergistic enhancement of the activity of rifampin. CRL-1072 was synthesized to have an optimal structure for antimicrobic effects and greater purity. Its MIC for MAI in broth was greater than 100 μg/ml. Surprisingly, its MIC for MAI growing in human U937 monocytoid cells was much lower, 5 μg/ml. A still lower concentration, 0.1 μg/ml, produced synergistic enhancement of the activities of clarithromycin, rifampin, amikacin, streptomycin, and clindamycin, but not isoniazid, against MAI infecting monocytoid cells. Mice tolerated injection of doses of CRL-1072 as high as 125 mg/kg of body weight. Pharmacokinetic analysis revealed that the copolymer had an elimination half-life of 60 h and suggested dosing regimens that might produce therapeutic concentrations in tissue. In a mouse model of acute MAI infection, CRL-1072 significantly enhanced the bactericidal activities of clarithromycin and rifampin when it was administered at 1.0 mg/kg intravenously (i.v.) three times per week. CRL-1072 given i.v. or orally also enhanced the bactericidal activity of clindamycin against MAI.
Novel Streptomycin and Spectinomycin Resistance Gene as a Gene Cassette within a Class 1 Integron Isolated from
Escherichia coli
Authors: Sandvang Dorthe 
Published: October 2018

ABSTRACT

The
aadA
genes, encoding resistance to streptomycin and spectinomycin, have been found as gene cassettes in different gram-negative and gram-positive bacterial species. The present study has revealed the sequence of a new gene,
aadA5
, integrated as a gene cassette together with the trimethoprim resistance gene
dfr7
in a class 1 integron. The integron was located on a plasmid and was identified in a pathogenic porcine
Escherichia coli
isolate.
In Vitro Activities of Ketolide HMR3647, Macrolides, and Other Antibiotics against
Lactobacillus
,
Leuconostoc
, and
Pediococcus
Isolates
Authors: Zarazaga M. , Sáenz Y. , Portillo A. , Tenorio C. , Ruiz-Larrea F. , Del Campo R. , Baquero F. , Torres C. 
Published: October 2018

ABSTRACT

Testing of susceptibility to 13 antibiotics was performed with 90 isolates of
Lactobacillus
,
Leuconostoc
, and
Pediococcus
. MICs at which 90% of the isolates tested were inhibited by HMR3647, erythromycin, and ciprofloxacin were 0.015, 0.125 and 32 μg/ml, respectively. The penicillin MIC was ≥16 μg/ml against 26.2% of the studied
Lactobacillus
sp. isolates and 50% of
Lactobacillus plantarum
. HMR3647 showed excellent activity against these genera.
A Rapid Non-Culture-Based Assay for Clinical Monitoring of Phenotypic Resistance of Human Immunodeficiency Virus Type 1 to Lamivudine (3TC)
Authors: García Lerma J. Gerardo , Schinazi Raymond F. , Juodawlkis Amy S. , Soriano Vincent , Lin Yulin , Tatti Kathleen , Rimland David , Folks Thomas M. , Heneine Walid 
Published: October 2018

ABSTRACT
Monitoring for lamivudine (3TC) resistance is important both for the clinical management of human immunodeficiency virus type 1 (HIV-1)-infected patients treated with 3TC and for surveillance of transmission of 3TC-resistant HIV-1. We developed a novel non-culture-based assay for the rapid analysis of phenotypic resistance to 3TC of HIV-1 in plasma. The assay measures the susceptibility of HIV-1 reverse transcriptase (RT) activity to 3TC triphosphate (3TC-TP) in plasma. RT detection was done by the Amp-RT assay, an ultrasensitive PCR-based RT assay. Under our assay conditions, we found that 5 μM 3TC-TP inhibited RT activity from wild-type (WT), zidovudine-resistant, or nevirapine-resistant HIV-1 but not from HIV-1 carrying either the M184V mutation or multidrug (MD) resistance mutations (77L/116Y/151M or 62V/75I/77L/116Y/151M). Mixing experiments showed a detection threshold of 10% 3TC-resistant virus (M184V) in a background of WT HIV-1. To validate the assay for the detection of phenotypic resistance of HIV-1 to 3TC in plasma samples, HIV-1 RT in 30 plasma specimens collected from 15 patients before and during therapy with 3TC was tested for evidence of phenotypic resistance by the Amp-RT assay. The results were compared with those of genotypic analysis. The RT in 12 samples was found to be 3TC sensitive, while the RT in 18 samples had evidence of phenotypic resistance. All 12 samples with 3TC-sensitive RT had WT genotypes at codon 184 and were retrieved before treatment with 3TC. In contrast, all 18 specimens with 3TC-resistant RT were posttherapy samples. This assay provides a simple, rapid, and reliable method for the detection of phenotypic resistance of HIV-1 to 3TC in plasma.