bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Low-Dose Dopamine in Preventing Amphotericin B Nephrotoxicity in Bone Marrow Transplant Patients and Leukemia Patients
Authors: Camp Mary J. , Wingard John R. , Gilmore Claire E. , Lin Lillian S. , Dix Suzanne P. , Davidson Terry G. , Geller Robert B. 
Published: October 2018

ABSTRACT

This study evaluated the efficacy of low-dose dopamine for prevention of amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Seventy-one patients undergoing cytoreductive therapy who required amphotericin B were randomly assigned in an unblinded fashion to a group receiving continuous-infusion low-dose dopamine (3 μg/kg/min) or a group receiving no dopamine. Amphotericin B was dosed at 0.5 or 1.0 mg/kg/day based on computerized tomography scan results or presence of positive blood cultures. No patient received saline boluses. The rate of nephrotoxicity, severity as graded by Southwest Oncology Group toxicity criteria, and time to each grade of nephrotoxicity were compared between the two groups. Eighty percent of the no-dopamine group and 66.7% of the dopamine group developed nephrotoxicity, defined as a 1.5-fold or greater increase in baseline serum creatinine level (
P
= 0.20). No statistical difference was noted at any grade of nephrotoxicity between the two groups. Thirty-four percent of patients in the no-dopamine group versus 17.6% in the dopamine group had a 2.5-fold or greater increase in serum creatinine level, which was not statistically significant (
P
= 0.0888). Ten patients developed grade IV nephrotoxicity and were withdrawn from the study, 7 in the no-dopamine group and 3 in the dopamine group (
P
= 0.19). The time to each grade of nephrotoxicity was also not significantly different for the two groups. Eleven adverse drug reactions were reported in the dopamine group in comparison to one in the no-dopamine group. Thus, dopamine offers little in the way of prevention of nephrotoxicity associated with amphotericin B therapy. Although the significance of drug reactions in the dopamine group is not clearly established due to lack of cardiac monitoring in the no-dopamine group, dopamine therapy is not without complications.
Novel OXA-10-Derived Extended-Spectrum β-Lactamases Selected In Vivo or In Vitro
Authors: Mugnier P. , Casin I. , Bouthors A. T. , Collatz E. 
Published: October 2018

ABSTRACT

A clinical isolate of
Pseudomonas aeruginosa
, PAe191, was found to be highly resistant to all anti-
Pseudomonas
β-lactam antibiotics (except imipenem) and resistant also to aminoglycosides. It produced a β-lactamase (with an apparent pI of 7.6) which was not inhibited by clavulanic acid. Cloning and characterization of the β-lactamase gene showed that it coded for a novel extended-spectrum OXA-10 variant, called OXA-19, which differed from OXA-10 by nine amino acids and from OXA-13 by two, i.e., Asn in position 73 (Asn73) instead of Ser and Asp157 instead of Gly. Asparagine in position 157 is implicated in resistance to ceftazidime, while the amino acid in position 73, in this variant, seems to condition the level of resistance to penicillins. The
oxa19
gene was found to be inserted, in a typical integron structure, immediately downstream from an
aac
(
6
′)-
Ib
gene coding for an aminoglycoside acetyltransferase variant, which was called AAC(6′)-Ib
9
.
Pharmacokinetics, Distribution in Serum Lipoproteins and Tissues, and Renal Toxicities of Amphotericin B and Amphotericin B Lipid Complex in a Hypercholesterolemic Rabbit Model: Single-Dose Studies
Authors: Wasan Kishor M. , Kennedy Allison L. , Cassidy Shawn M. , Ramaswamy Manisha , Holtorf Lorilynne , Chou Jenny Wen-Lin , Pritchard P. Haydn 
Published: October 2018

ABSTRACT
The purpose of this study was to determine if a relationship exists among total serum and lipoprotein cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the serum pharmacokinetics of AmpB in hypercholesterolemic rabbits administered AmpB and AmpB lipid complex (ABLC). After 10 days of cholesterol-enriched diet (0.50% [wt/vol]) or regular rabbit diet (control), each rabbit was administered a single intravenous bolus of AmpB or ABLC (1.0 mg/kg of body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, kidney toxicity, and serum lipoprotein distribution. Rabbits were humanely sacrificed after all blood samples were obtained, and tissues were harvested for drug analysis. Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total serum cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with levels in rabbits on a regular diet. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered AmpB. However, the magnitude of this increase was 2.5-fold greater in cholesterol-fed rabbits than in regular diet-fed rabbits. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered ABLC. Whereas AmpB pharmacokinetics were significantly altered in cholesterol-fed rabbits administered free AmpB, similar AmpB pharmacokinetics were observed in both rabbit groups administered ABLC. Renal AmpB levels were significantly increased in cholesterol-fed rabbits administered AmpB compared with those in all other groups. Hepatic and lung AmpB levels were elevated in cholesterol-fed rabbits administered free AmpB compared to controls. In addition, hepatic, lung, and spleen AmpB levels were significantly decreased in cholesterol-fed rabbits administered ABLC compared to controls. An increased percentage of AmpB was recovered in LDL–very-low-density lipoprotein fraction when free AmpB was administered to cholesterol-fed rabbits compared with those in all other groups. These findings suggest that increases in cholesterol, specifically, LDL cholesterol levels, modify the disposition and renal toxicity of free AmpB. However, the pharmacokinetics and renal toxicity of ABLC were independent of elevations in total and LDL cholesterol levels.
Antibacterial Effects of Levofloxacin, Erythromycin, and Rifampin in a Human Monocyte System against
Legionella pneumophila
Authors: Baltch Aldona L. , Smith Raymond P. , Franke Mary A. , Michelsen Phyllis B. 
Published: October 2018

ABSTRACT

The antibacterial activities of levofloxacin, erythromycin, and rifampin against intracellular
Legionella pneumophila
L-1033, serogroup 1, were studied. In an in vitro system utilizing adherent human monocytes,
L. pneumophila
L-1033, a phagocytosis time period of 1 h, and antibiotic (levofloxacin, erythromycin, and/or rifampin) at 1 to 10 times the MIC, the CFU/ml values for the monocyte lysate were determined during 0- to 4-day time periods. The decrease in CFU/ml with levofloxacin at pH 7.4 was rapid, occurring within 24 h, and was drug concentration dependent (
P
< 0.01). The decrease in CFU with rifampin was first observed at 48 h (
P
< 0.01), while only a minimal decrease in CFU/ml was observed with erythromycin. Combination of levofloxacin and rifampin and of levofloxacin and erythromycin at ten times their MICs significantly decreased the CFU/ml value (
P
< 0.01), to the value attained by levofloxacin alone, while combination of rifampin and erythromycin did not. Removal of levofloxacin after 24 h of incubation resulted in regrowth of
L. pneumophila
L-1033, while a continued slow decrease in CFU/ml was seen following rifampin removal; CFU/ml values were unaffected by the removal of erythromycin. At 4 days, and even in assays performed following antibiotic removal, the CFU/ml value continued to be lower in the levofloxacin and rifampin assays than in the assays with erythromycin. Levofloxacin had a significantly higher bactericidal activity against
L. pneumophila
L-1033 than erythromycin or rifampin. In these assays, the addition of erythromycin or rifampin did not affect the antibacterial activity of levofloxacin.
Characterization of a Chromosomal Gene Encoding Type B β-Lactamase in Phage Group II Isolates of
Staphylococcus aureus
Authors: Voladri Rama Kishan R. , Kernodle Douglas S. 
Published: October 2018

ABSTRACT

In contrast to most
Staphylococcus aureus
isolates in which the gene for staphylococcal β-lactamase (
blaZ
) is plasmid borne, isolates typeable by group II bacteriophages frequently carry
blaZ
on the chromosome. Furthermore, the chromosomal gene encodes the type B variant of staphylococcal β-lactamase for which the nucleotide and deduced amino acid sequences have not yet been reported. To better understand β-lactamase production among phage group II staphylococci and the nature of the type B β-lactamase, we determined the type and amount of enzyme produced by 24 phage group II isolates. Of these isolates, 1 did not produce β-lactamase, 8 produced the type B enzyme, and 15 produced the type C enzyme. In all eight type B β-lactamase-producing isolates,
blaZ
was located on the chromosome. This was in contrast to the type C β-lactamase-producing isolates, in which
blaZ
was located on a 21-kb plasmid. The nucleotide sequence corresponding to the leader peptide and the N-terminal 85% of the mature exoenzyme form of type B
S. aureus
was determined. The deduced amino acid sequence revealed 3 residues in the leader peptide and 12 residues in the exoenzyme portion of the β-lactamase that differ from the prototypic type A β-lactamase sequence. These include the serine-to-asparagine change at residue 216 found in the kinetically similar type C enzyme, a threonine-to-lysine change at residue 128 close to the SDN loop (residues 130 to 132), and several substitutions not found in any of the other staphylococcal β-lactamases. In summary, modern isolates of
S. aureus
typeable by group II phages produce type B or type C staphylococcal β-lactamase. The type B gene resides on the chromosome and has a sequence that, when compared to the sequences of the other staphylococcal β-lactamases, corresponds well with its kinetic properties.
The Antiherpesvirus Activity of H2G [(
R
)-9-[4-Hydroxy-2-(Hydroxymethyl)Butyl]Guanine] Is Markedly Enhanced by the Novel Immunosuppressive Agent Mycophenolate Mofetil
Authors: Neyts Johan , Andrei Graciela , De Clercq Erik 
Published: October 2018

ABSTRACT

Mycophenolate mofetil (MMF) has been approved as an immunosuppressive agent in kidney transplant recipients and may thus be used concomitantly with antiherpetic agents, which are used for the treatment of intercurrent herpesvirus infections. We have recently demonstrated that MMF and its parent compound mycophenolic acid (MPA), which is a potent inhibitor of IMP dehydrogenase, potentiate the antiherpesvirus activity of acyclovir, ganciclovir, and penciclovir. We have now evaluated the antiviral efficacy of the combination of MPA and the novel antiherpesvirus agent H2G [(
R
)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine]. When combined with H2G, MPA (at concentrations ranging from 0.25 to 10 μg/ml, which are readily attainable in human plasma) markedly potentiated the antiviral efficacy of H2G against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), as reflected by a 10- to 150-fold decrease in the 50% effective concentration. Moreover, the activity of H2G against a thymidine kinase-deficient strain of HSV-1 (TK
−
HSV-1) was increased more than 2,500-fold when combined with MPA. MPA by itself had little or no effect on the replication of these viruses. Similar observations were made for varicella-zoster virus. Also, ribavirin (another inhibitor of IMP dehydrogenase) caused a marked enhancement of the activity of H2G against HSV-1 (10-fold), HSV-2 (10-fold), and TK
−
HSV-1 (>185-fold). Exogenously added guanosine reversed the potentiating effects of MPA on the antiviral activity of H2G, indicating that this potentiating effect resulted from a depletion of the endogenous dGTP pools, thus favoring the inhibitory action of the H2G triphosphate on the viral DNA polymerase.
An
ampD
Gene in
Pseudomonas aeruginosa
Encodes a Negative Regulator of AmpC β-Lactamase Expression
Authors: Langaee Taimour Yousef , Dargis Michèle , Huletsky Ann 
Published: October 2018

ABSTRACT

The
ampD
and
ampE
genes of
Pseudomonas aeruginosa
PAO1 were cloned and characterized. These genes are transcribed in the same orientation and form an operon. The deduced polypeptide of
P. aeruginosa ampD
exhibited more than 60% similarity to the AmpD proteins of enterobacteria and
Haemophilus influenzae
. The
ampD
product transcomplemented
Escherichia coli ampD
mutants to wild-type β-lactamase expression.
Macrolide Susceptibility and β-Lactamase Production among
Haemophilus influenzae
Isolates in the United States, 1996–1997
Authors: Hogan Patricia A. , Sheehan Daniel J. 
Published: October 2018

ABSTRACT

In 1996 and 1997, 68 hospital laboratories throughout the United States determined the β-lactamase production and susceptibility to macrolides of 1,998 isolates of
Haemophilus influenzae
obtained from patients with community-acquired respiratory tract infections. The MICs at which 90% of the isolates are inhibited of azithromycin, erythromycin, and clarithromycin were 4, 8, and 16 μg/ml, respectively. By National Committee for Clinical Laboratory Standards interpretive criteria, 99 and 78% of the isolates were susceptible to azithromycin and clarithromycin, respectively. The prevalence of β-lactamase production was 32%.
In Vitro Activities of Several Diaminomethylpyridopyrimidines against
Mycobacterium avium
Complex
Authors: Shoen Carolyn M. , Choromanska Olga , Reynolds Robert C. , Piper James R. , Johnson Cheryl A. , Cynamon Michael H. 
Published: October 2018

ABSTRACT

Three recently synthesized dihydrofolate reductase (DHFR) inhibitors designated SoRI 8890, 8895, and 8897 were evaluated for their in vitro activities against 25 isolates of
Mycobacterium avium
complex. The MICs at which 50 and 90% of isolates were inhibited were 1 and 2, 4 and 8, and 4 and 8 μg/ml for SoRI 8890, 8895, and 8897, respectively. Although the addition of dapsone at 0.5 μg/ml did not significantly enhance the in vitro activities of these compounds, their activities alone were comparable to, if not better than, results seen with other DHFR inhibitors, such as pyrimethamine or WR99210.
Examination of Methicillin-Resistant and Methicillin-Susceptible
Staphylococcus aureus
Mutants with Low-Level Fluoroquinolone Resistance
Authors: Sulavik Mark C. , Barg Neil L. 
Published: October 2018

ABSTRACT

For
Staphylococcus aureus
, stepwise mutations result in high-level quinolone resistance. Methicillin-resistant and -susceptible quinolone-resistant, first-step mutants generated in vitro were obtained and found to be no different than those recovered from murine abscesses. Approximately 10% of all first-step mutants were resistant to ethidium bromide, and selected strains had mutations that mapped to
flqB
. NorA-mediated resistance among first-step mutants may be more prevalent than previously reported.
In Vitro Activities of Cefminox against Anaerobic Bacteria Compared with Those of Nine Other Compounds
Authors: Hoellman Dianne B. , Spangler Sheila K. , Jacobs Michael R. , Appelbaum Peter C. 
Published: October 2018

ABSTRACT

The agar dilution MIC method was used to test the activity of cefminox, a β-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active β-lactam, with an MIC at which 50% of isolates are inhibited (MIC
50
) of 1.0 μg/ml and an MIC
90
of 16.0 μg/ml. Other β-lactams were less active, with respective MIC
50
s and MIC
90
s of 2.0 and 64.0 μg/ml for cefoxitin, 2.0 and 128.0 μg/ml for cefotetan, 2.0 and 64.0 μg/ml for moxalactam, 4.0 and >128.0 μg/ml for ceftizoxime, 16.0 and >128.0 μg/ml for cefotiam, 8.0 and >128.0 μg/ml for cefamandole, and 4.0 and 128.0 μg/ml for cefoperazone. The clindamycin MIC
50
and MIC
90
were 0.5 and 8.0 μg/ml, respectively, and the metronidazole MIC
50
and MIC
90
were 1.0 and 4.0 μg/ml, respectively. Cefminox was especially active against
Bacteroides fragilis
(MIC
90
, 2.0 μg/ml),
Bacteroides thetaiotaomicron
(MIC
90
, 4.0 μg/ml), fusobacteria (MIC
90
, 1.0 μg/ml), peptostreptococci (MIC
90
, 2.0 μg/ml), and clostridia, including
Clostridium difficile
(MIC
90
, 2.0 μg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4× the MIC and cefoperazone at 8× the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2× the MIC produced the most rapid effect, with 90% killing of all strains.
Diversity of VanA Glycopeptide Resistance Elements in Enterococci from Humans and Nonhuman Sources
Authors: Woodford Neil , Adebiyi Antoinette-Mary A. , Palepou Marie-France I. , Cookson Barry D. 
Published: October 2018

ABSTRACT

Elements mediating VanA glycopeptide resistance in 106 diverse enterococci from humans and nonhuman sources were compared with the prototype VanA transposon, Tn
1546
, in
Enterococcus faecium
BM4147. The isolates included 64 from individual patients at 15 hospitals in the United Kingdom (isolated between 1987 and 1996) and 42 from nonhuman sources in the United Kingdom (27 from raw meat, 7 from animal feces, and 8 from sewage). VanA elements were assigned to 24 groups (designated groups A to X) with primers that amplified 10 overlapping fragments of Tn
1546
. Ten groups of elements were found only in human enterococci, eight groups of elements were unique to nonhuman strains, and six groups of elements were common in enterococci from all sources. Elements indistinguishable from Tn
1546
(group A) were observed more frequently in enterococci from nonhuman sources (34 versus 9%) but were identified in enterococci that caused outbreaks in hospital patients between 1987 and 1995. The most common group found in human enterococci (group H; 33%) was rarely observed in enterococci from other sources (5%). Group H elements differed from Tn
1546
in three regions and included a novel insertion sequence, designated IS
1542
, between
orf2
and
vanR
. The VanA elements of 14 other groups had a similar insertion at this position and/or distinct insertions at other positions. We conclude that VanA elements in enterococci are heterogeneous, although all show regions of homology with Tn
1546
. Furthermore, the elements most common among the human and nonhuman enterococci studied were different. This approach may be useful for monitoring the evolution of VanA resistance and may also be applicable in local “snapshot” epidemiological studies. However, as transposition events involving insertion sequences accounted for the differences observed between several groups, the stability of the elements must be assessed before their true epidemiological significance can be determined.
In Vitro Antimalarial Activity of a New Organometallic Analog, Ferrocene-Chloroquine
Authors: Domarle O. , Blampain G. , Agnaniet H. , Nzadiyabi T. , Lebibi J. , Brocard J. , Maciejewski L. , Biot C. , Georges A. J. , Millet P. 
Published: October 2018

ABSTRACT

The in vitro activities of new organometallic chloroquine analogs, based on 4-amino-quinoleine compounds bound to a molecule of ferrocene, were evaluated against chloroquine-susceptible, chloroquine-intermediate, and chloroquine-resistant, culture-adapted
Plasmodium falciparum
lineages by a proliferation test. One of the ferrocene analogs totally restored the activity of chloroquine against chloroquine-resistant parasites. This compound, associated with tartaric acid for better solubility, was highly effective. The role of the ferrocene in reversing chloroquine resistance is discussed, as is its potential use for human therapy.
Covalent Polymyxin B Conjugate with Human Immunoglobulin G as an Antiendotoxin Reagent
Authors: Drabick Joseph J. , Bhattacharjee Apurba K. , Hoover David L. , Siber George E. , Morales Vivian E. , Young Lynnette D. , Brown Scott L. , Cross Alan S. 
Published: October 2018

ABSTRACTPolymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at clinically utilized doses, thereby limiting its utility as a therapeutic antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity profile of PMB by covalently linking it to a human immunoglobulin G (IgG) carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted with lipid A and J5 lipopolysaccharide in Western blot assays in a manner comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin-neutralizing activity compared to that of unbound PMB as evidenced by its dose-dependent inhibition of tumor necrosis factor release by endotoxin-stimulated human monocytes in vitro; unconjugated IgG had no activity. By this assay, the PMB-IgG conjugate was determined to have approximately 3.0 μg of bound functional PMB per 100 μg of total protein of conjugate (five molecules of PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against clinical strains ofEscherichia coli,Pseudomonas aeruginosa, andKlebsiella pneumoniaerelative to unconjugated IgG with MBCs of <4 μg of conjugate per ml for each of the tested strains. The conjugate appeared to be nontoxic at the highest doses deliverable and provided statistically significant protection from death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose-dependent fashion when administered prophylactically 2 h before challenge. However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged with endotoxin 2 h after administration. This suggests that these reagents can play a role in prophylaxis but not in therapy of sepsis. These experiments demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as evidenced by its endotoxin-neutralizing activity both in vitro and in vivo. Further work is required to define the role that this or related conjugate compounds may play in the prophylaxis of endotoxin-mediated disease.