bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Bacteremia in Rabbit Fetuses despite Maternal Antibiotic Therapy in a Novel Intrauterine-Infection Model
Authors: Gras-Le Guen C. , Debillon T. , Toquet C. , Jarry A. , Winer N. , Jacqueline C. , Kergueris M. F. , Bingen E. , Roze J. C. , Potel G. , Bugnon D. 
Published: June 2003

ABSTRACTThe effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model ofEscherichia colimaternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, quantitative blood cultures, fetal histology in treated versus untreated groups, and maternal and fetal antibiotic concentrations in plasma in treated animals. Antibiotic therapy led to dramatic improvement in maternal outcome (100% survival versus 100% death in the untreated group in association with maternal septicemia). Fetal survival also improved, with the two-drug combination providing a more potent effect. After 3 days of treatment, 32% of fetuses survived with one-drug therapy and 62% with two-drug therapy (Yates corrected χ2,P< 0.05). In untreated animals, bacterial counts in blood cultures increased rapidly during the first 24 h up to 8.1 ± 0.5 log CFU/ml, but remained relatively constant at all times with antibiotic treatment: 4.5 ± 0.7 log CFU/ml at the start of treatment and 6.2 ± 0.4 and 5.2 ± 0.9 log CFU/ml after 72 h for one- and two-drug therapy, respectively (data are means ± standard deviations). The failure of animals to be cured after 3 days of treatment was not due to an inadequate concentration of ceftriaxone, as the residual level in fetal serum at sacrifice was more than 1,000 times the MIC of the microbe. Unexpectedly, inflammation in fetal lung decreased in the treated group after as little as 24 h of antibiotic therapy, despite persistent bacteremia. Although maternal outcome improved and drug concentrations were above the MIC, the treatment did not achieve sterilization of fetuses in utero for this rabbitE. colimaternofetal infection. However, fetal survival showed some improvement, and the histologic features of lung inflammation were reduced.
Effects of Ritonavir on Indinavir Pharmacokinetics in Cerebrospinal Fluid and Plasma
Authors: Haas David W. , Johnson Benjamin , Nicotera Janet , Bailey Vicki L. , Harris Victoria L. , Bowles Farideh B. , Raffanti Stephen , Schranz Jennifer , Finn Tyler S. , Saah Alfred J. , Stone Julie 
Published: June 2003

ABSTRACT

Therapeutic control of human immunodeficiency virus type 1 (HIV-1) in peripheral compartments does not assure control in the central nervous system. Inadequate drug penetration may provide a sanctuary from which resistant virus can emerge or allow development of psychomotor abnormalities. To characterize the effect of ritonavir on indinavir disposition into cerebrospinal fluid, seven HIV-infected adults underwent intensive sampling at steady-state while receiving twice-daily indinavir (800 mg) and ritonavir (100 mg). Serial cerebrospinal fluid and plasma samples were obtained at 10 time points from each subject. Free indinavir accounted for 98.6% of drug in cerebrospinal fluid and 55.9% in plasma. Mean cerebrospinal fluid
C
max
,
C
min
, and area under the concentration-time curve from 0 to 12 h (AUC
0-12
) values for free indinavir were 735 nM, 280 nM, and 6,502 nM h
−1
, respectively, and the free levels exceeded 100 nM in every sample. The cerebrospinal fluid/plasma AUC
0-12
ratio for free indinavir was 17.5% ± 6.4%. This ratio was remarkably similar to results obtained in a previous study in which subjects received indinavir without ritonavir, indicating that ritonavir did not have a substantial direct effect on the barrier to indinavir penetration into cerebrospinal fluid. Low-dose ritonavir increases cerebrospinal fluid indinavir concentrations substantially more than 800 mg of indinavir given thrice daily without concomitant ritonavir, despite a lower total daily indinavir dose.
Telithromycin- and Fluoroquinolone-Resistant
Streptococcus pneumoniae
in Taiwan with High Prevalence of Resistance to Macrolides and β-Lactams: SMART Program 2001 Data
Authors: Hsueh Po-Ren , Teng Lee-Jene , Wu Tsu-Lan , Yang Dine , Huang Wen-Kuei , Shyr Jainn-Ming , Chuang Yin-Ching , Wan Jen-Hsien , Yan Jing-Jou , Lu Jang-Jih , Wu Jiunn-Jong , Ko Wen-Chien , Chang Feng-Yee , Yang Yi-Chueh , Lau Yeu-Jun , Liu Yung-Ching , Lee Chun-Ming , Leu Hsieh-Shong , Liu Cheng-Yi , Luh Kwen-Tay 
Published: June 2003

ABSTRACT

There is a high prevalence of β-lactam- and macrolide-resistant
Streptococcus pneumoniae
in Taiwan. To understand the in vitro susceptibilities of recent isolates of
S. pneumoniae
to fluoroquinolones and telithromycin (which is not available in Taiwan), the MICs of 23 antimicrobial agents for 936 clinical isolates of
S. pneumoniae
isolated from different parts of Taiwan from 2000 to 2001 were determined by the agar dilution method. Overall, 72% of isolates were not susceptible to penicillin (with 61% being intermediate and 11% being resistant) and 92% were resistant to erythromycin. Telithromycin MICs were ≥1 μg/ml for 16% of the isolates, and for 99% of these isolates the MICs of all macrolides tested were ≥256 μg/ml; all of these isolates had the constitutive macrolide-lincosamide-streptogramin B phenotype. Eighty-eight percent of the isolates were resistant to three or more classes of drugs. The ciprofloxacin MICs were ≥4 μg/ml for six (0.6%) isolates from five patients collected in 2000 and 2001, and the levofloxacin MICs were ≥8 μg/ml for five of these isolates. Seven isolates for which ciprofloxacin MICs were ≥4 μg/ml, including one isolate recovered in 1999, belonged to three serotypes (serotype 19F, five isolates; serotype 23A, one isolate; and serotype 23B, one isolate). The isolates from the six patients for which ciprofloxacin MICs were ≥4 μg/ml had different pulsed-field gel electrophoresis profiles and random amplified polymorphic DNA patterns, indicating that no clonal dissemination occurred over this time period. Despite the increased rate of fluoroquinolone use, the proportion of pneumococcal isolates for which ciprofloxacin MICs were elevated (≥4 μg/ml) remained low. However, the occurrence of telithromycin resistance is impressive and raises concerns for the future.
Telithromycin and Quinupristin-Dalfopristin Resistance in Clinical Isolates of
Streptococcus pyogenes
: SMART Program 2001 Data
Authors: Hsueh Po-Ren , Teng Lee-Jene , Lee Chun-Ming , Huang Wen-Kuei , Wu Tsu-Lan , Wan Jen-Hsien , Yang Dine , Shyr Jainn-Ming , Chuang Yin-Ching , Yan Jing-Jou , Lu Jang-Jih , Wu Jiunn-Jong , Ko Wen-Chien , Chang Feng-Yee , Yang Yi-Chueh , Lau Yeu-Jun , Liu Yung-Ching , Leu Hsieh-Shong , Liu Cheng-Yi , Luh Kwen-Tay 
Published: June 2003

ABSTRACT

This study evaluated the current status of antimicrobial resistance in clinical isolates of
Streptococcus pyogenes
in Taiwan as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. In 2001, 419 different isolates of
S. pyogenes
, including 275 from respiratory secretions, 87 from wound pus, and 31 from blood, were collected from nine hospitals in different parts of Taiwan. MICs of 23 antimicrobial agents were determined at a central location by the agar dilution method. All of the isolates were susceptible to penicillin (MIC at which 90% of the isolates were inhibited [MIC
90
], ≤0.03 μg/ml), cefotaxime (MIC
90
, ≤0.03 μg/ml), cefepime (MIC
90
, 0.06 μg/ml), meropenem (MIC
90
, ≤0.03 μg/ml), moxifloxacin (MIC
90
, 0.25 μg/ml), vancomycin (MIC
90
, 0.5 μg/ml), and linezolid (MIC
90
, 1 μg/ml). Overall, 78% of isolates were not susceptible to erythromycin (54% were intermediate, and 24% were resistant), and 5% were not susceptible to clindamycin. Of the 101 erythromycin-resistant isolates, 80.2% exhibited the M phenotype (
mefA
gene positive), 18.9% exhibited the cMLS (constitutive resistance to macrolides-lincosamides-streptogramin B [MLS]) phenotype (
ermB
gene positive), and 1% exhibited the iMLS (inducible resistance to MLS) phenotype (
ermB
gene positive). Fluoroquinolones (sitafloxacin > moxifloxacin > ciprofloxacin = levofloxacin = gatifloxacin > gemifloxacin) demonstrated potent activity against nearly all of the isolates of
S. pyogenes
tested. Thirty-two isolates (8%) were not susceptible to quinupristin-dalfopristin. Seventeen percent of isolates had telithromycin MICs of ≥1 μg/ml, and all of these isolates exhibited erythromycin MICs of ≥32 μg/ml. The high prevalence of resistance to telithromycin (which is not available in Taiwan) limits its potential use in the treatment of
S. pyogenes
infections, particularly in areas with high rates of macrolide resistance.
Effect of Calcium Carbonate on Bioavailability of Orally Administered Gemifloxacin
Authors: Pletz M. W. , Petzold P. , Allen A. , Burkhardt O. , Lode H. 
Published: June 2003

ABSTRACT

We investigated the effect of calcium carbonate on the oral bioavailability of gemifloxacin. Gemifloxacin was administered alone, 2 h before, simultaneously, or 2 h after calcium carbonate in 16 volunteers. Data for 320 mg of gemifloxacin alone were as follows: maximum concentration of drug in serum (
C
max
),13 μg/ml; half-life, 7.33 h; and area under the concentration-time curve from 0 h to infinity (AUC
∞
), 6.79 μg · h/ml. Only simultaneous coadministration of calcium carbonate reduced
C
max
(−17%) and AUC
∞
(−21%) significantly.
Isolation and Molecular Characterization of Nalidixic Acid-Resistant Extraintestinal Pathogenic
Escherichia coli
from Retail Chicken Products
Authors: Johnson James R. , Murray Andrew C. , Gajewski Abby , Sullivan Maureen , Snippes Paula , Kuskowski Michael A. , Smith Kirk E. 
Published: June 2003

ABSTRACT

Fluoroquinolone use in poultry production may select for resistant
Escherichia coli
that can be transmitted to humans. To define the prevalence and virulence potential of poultry-associated, quinolone-resistant
E. coli
in the United States, 169 retail chicken products from the Minneapolis-St. Paul area (1999 to 2000) were screened for nalidixic acid (Nal)-resistant
E. coli
. Sixty-two (37%) products yielded Nal-resistant
E. coli
. From 55 products that yielded both Nal-resistant and susceptible
E. coli
, two isolates (one resistant, one susceptible) per sample were further characterized. Twenty-three (21%) of the 110
E. coli
isolates (13 resistant, 10 susceptible) satisfied criteria for extraintestinal pathogenic
E. coli
(ExPEC), i.e., exhibited ≥2 of
pap
(P fimbriae),
sfa/foc
(S/F1C fimbriae),
afa/dra
(Dr binding adhesins),
iutA
(aerobactin receptor), and
kpsMT
II (group 2 capsule synthesis). Compared with other isolates, ExPEC isolates more often derived from virulence-associated
E. coli
phylogenetic groups B2 or D (74% versus 32%;
P
< 0.001) and exhibited more ExPEC-associated virulence markers (median, 10.0 versus 4.0;
P
< 0.001). In contrast, the Nal-resistant and -susceptible populations were indistinguishable according to all characteristics analyzed, including pulsed-field gel electrophoresis profiles. These findings indicate that Nal-resistant
E. coli
is prevalent in retail poultry products and that a substantial minority of such strains represent potential human pathogens. The similarity of the Nal-resistant and -susceptible populations suggests that they derive from the same source population, presumably the avian fecal flora, with Nal resistance emerging by spontaneous mutation as a result of fluoroquinolone exposure.
High-Level β-Lactam Resistance Associated with Acquired Multidrug Resistance in
Helicobacter pylori
Authors: Kwon Dong H. , Dore M. P. , Kim J. J. , Kato M. , Lee M. , Wu J. Y. , Graham D. Y. 
Published: June 2003

ABSTRACT

Four clinical
Helicobacter pylori
isolates with high-level resistance to β-lactams exhibited low- to moderate-level resistance to the structurally and functionally unrelated antibiotics ciprofloxacin, chloramphenicol, metronidazole, rifampin, and tetracycline. This pattern of multidrug resistance was transferable to susceptible
H. pylori
by natural transformation using naked genomic DNA from a clinical multidrug-resistant isolate. Acquisition of the multidrug resistance was also associated with a change in the genotype of the transformed multidrug-resistant
H. pylori
. DNA sequence analyses of the gene encoding penicillin binding protein 1A (PBP 1A) showed 36 nucleotide substitutions resulting in 10 amino acid changes in the C-terminal portion (the putative penicillin binding domain). Acquisition of β-lactam resistance was consistently associated with transfer of a mosaic block containing the C-terminal portion of PBP 1A. No changes of genes
gyrA
,
rpoB
,
rrn16S
,
rdxA
, and
frxA,
and nine other genes (
ftsI
,
hcpA
,
llm
,
lytB
,
mreB
,
mreC
,
pbp2
,
pbp4
, and
rodA1
) encoding putative PBPs or involved in cell wall synthesis were found among the transformed resistant
H. pylori
. Antibiotic accumulations of chloramphenicol, penicillin, and tetracycline were all significantly decreased in the natural and transformed resistant
H. pylori
compared to what was seen with susceptible
H. pylori.
Natural transformation also resulted in the outer membrane protein profiles of the transformed resistant
H. pylori
becoming similar to that of the clinical resistant
H. pylori
isolates. Overall, these results demonstrate that high-level β-lactam resistance associated with acquired multidrug resistance in clinical
H. pylori
is mediated by combination strategies including alterations of PBP 1A and decreased membrane permeability.
Survey of Plasmid-Associated Genetic Markers in
Enterobacteriaceae
with Reduced Susceptibilities to Cephalosporins
Authors: Preston Karen E. , Graffunder Eileen M. , Evans Ann M. , Venezia Richard A. 
Published: June 2003

ABSTRACT

Clinical isolates of
Enterobacteriaceae
with reduced susceptibilities to cephalosporins were collected from 1993 to 2000. The organisms were screened for the extended-spectrum β-lactamase (ESBL) phenotype, and plasmid extracts were screened for genetic markers by hybridization. A
bla
TEM
probe was derived from pUC19; other probes were derived from pACM1, the plasmid responsible for the first known appearance of an ESBL in our institution. These probes included
bla
SHV
,
int
,
aac(3)-Ia
,
dfrA1
, IS
6100
,
tetA
, IncM markers, and Anon 13, a marker for the
Klebsiella pneumoniae
chromosomal sequences that flank
bla
SHV-5
. There were 42 hybridization patterns among 237 isolates. Patterns designated pACM1-like occurred in 44% of the isolates (eight species) and were always associated with the clavulanic acid (CA)-susceptible ESBL phenotype. The TEM marker was not predictive of the ESBL phenotype. Mapping indicated the presence of an SHV marker and up to 7.5 kb of its flanking chromosomal sequences in three non-IncM plasmids obtained in transformation experiments. We theorize that this DNA segment spread to other plasmids from pACM1-like sources. CA insensitivity became more frequent with time and was usually associated with either the TEM marker or the absence of both
bla
markers. One plasmid-encoded enzyme with characteristics of an AmpC β-lactamase was observed in a transformant lacking both TEM and SHV markers. Although SHV type ESBLs were a continuing source of reduced susceptibility to cephalosporins in our institution, organisms with different resistance mechanisms were added to the hospital microflora in later years. These changes might be related, in part, to ESBL control strategies implemented in 1995.
In Vitro Activities of Benzimidazole
d
- and
l
-Ribonucleosides against Herpesviruses
Authors: Williams Stephanie L. , Hartline Caroll B. , Kushner Nicole L. , Harden Emma A. , Bidanset Deborah J. , Drach John C. , Townsend Leroy B. , Underwood Mark R. , Biron Karen K. , Kern Earl R. 
Published: June 2003

ABSTRACT

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and human herpesvirus 8 (HHV-8) are responsible for a number of clinical manifestations in both normal and immunocompromised individuals. The parent benzimidazole ribonucleosides evaluated in this series, 2-bromo-5,6-dichloro-1-(β-
d
-ribofuranosyl)benzimidazole (BDCRB) and maribavir (1263W94), are potent and selective inhibitors of human CMV replication. These nucleosides act by two different mechanisms. BDCRB blocks the processing and maturation of viral DNA, whereas 1263W94 inhibits the viral enzyme pUL97 and interferes with DNA synthesis. In the present study, we have evaluated the in vitro antiviral activity of BDCRB, an analog, GW275175X (175X), and 1263W94 against the replication of HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, and HHV-8. By using various methodologies, significant activity was observed against human CMV and EBV but not against HSV-1, HSV-2, VZV, HHV-6, or HHV-8. Plaque reduction assays performed on a variety of laboratory and clinical isolates of human CMV indicated that all strains, including those resistant to ganciclovir (GCV) and foscarnet, were sensitive to all three benzimidazole ribonucleosides, with mean 50% effective concentration values of about 1 to 5 μM compared to that of GCV at 6 μM. The toxicity of these compounds in tissue culture cells appeared to be similar to that observed with GCV. These results demonstrate that the benzimidazole ribonucleosides are active against human CMV and EBV and suggest that they may be useful for the treatment of infections caused by these herpesviruses.
Evaluation of Nucleoside Phosphonates and Their Analogs and Prodrugs for Inhibition of Orthopoxvirus Replication
Authors: Keith Kathy A. , Hitchcock Michael J. M. , Lee William A. , Holý Antonin , Kern Earl R. 
Published: June 2003

ABSTRACT

In the event of a bioterrorism attack using smallpox virus, there currently is no approved drug for the treatment of infections with this virus. We have reported previously that (
S
)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC) (also known as cidofovir [CDV]) has good activity against poxvirus infections; however, a major limitation is the requirement for intravenous administration. Two related acyclic nucleoside phosphonates (ANPs), adefovir (PMEA) and tenofovir (PMPA), are active against human immunodeficiency virus or hepatitis B virus but do not have activity against the orthopoxviruses. Therefore, we have evaluated a number of analogs and potential oral prodrugs of these three compounds for their ability to inhibit the replication of vaccinia virus or cowpox virus in tissue culture cells. The most-active compounds within the CDV series were (
S
)-HPMPA and (butyl
l
-alaninyl) cyclic HPMPC, with 50% effective concentrations (EC
50
s) from 4 to 8 μM, compared with 33 to 43 μM for CDV. Although PMEA itself was not active, adefovir dipivoxil {bis[(pivaloyl)oxymethyl] PMEA} and bis(butyl
l
-alaninyl) PMEA were active against both viruses, and bis(butyl
l
-alaninyl) PME-N6-(cyclopropyl)DAP and (isopropyl
l
-alaninyl)phenyl PME-N6-(cyclopropyl)DAP were the most active compounds tested, with EC
50
s of 0.1 to 2.6 μM. In the PMPA series, none of the analogs tested had significantly better activity than PMPA itself. These data indicate that a number of these ANP derivatives have activity against vaccinia virus and cowpox virus in vitro and should be evaluated for their efficacies in animal models.
Tolerability of Azithromycin as Malaria Prophylaxis in Adults in Northeast Papua, Indonesia
Authors: Taylor Walter R. , Richie Thomas L. , Fryauff David J. , Ohrt Colin , Picarima Helena , Tang Douglas , Murphy Gerald S. , Widjaja Hendra , Braitman David , Tjitra Emiliana , Ganjar Asep , Jones Trevor R. , Basri Hasan , Berman Josh 
Published: June 2003

ABSTRACT

Drug tolerability affects compliance. We evaluated the tolerability levels of azithromycin (750-mg loading dose plus 250 mg/day;
n
= 148 subjects), doxycycline (100 mg/day;
n
= 75), and placebo (
n
= 77) as prophylaxis against malaria in Indonesian adults over 20 weeks. Self-reported and elicited symptoms, health perception, hearing, hematology, and biochemistry were assessed. The loading dose was well tolerated. The frequencies (number per person-years [p-yr]) of all daily reported symptoms were similar in the three arms of the study: 40.2/p-yr for azithromycin, 39.7/p-yr for doxycycline, and 38.2/p-yr for placebo. Relative to those who received placebo, azithromycin recipients complained more often of heartburn (rate ratio = 10.5 [95% confidence interval, 2.8 to 88.1]), paresthesia (2.03 [1.08 to 4.24]), and mild (1.55 [1.01 to 2.48]) and severe (11.2 [1.34 to ∞]) itching but less often of fever (0.21 [0.09 to 0.49]) and tinnitus (0.09 [0.04 to 0.21]). Azithromycin recipients showed no evidence of clinical hearing loss or hematologic, hepatic, or renal toxicity. One azithromycin recipient developed an erythematous rash. Daily azithromycin was well tolerated by these Indonesian adults during 20 weeks of treatment.
Preclinical Assessment of the Efficacy of Mycograb, a Human Recombinant Antibody against Fungal HSP90
Authors: Matthews Ruth C. , Rigg Gordon , Hodgetts Samantha , Carter Tracey , Chapman Caroline , Gregory Carl , Illidge Chris , Burnie James 
Published: June 2003

ABSTRACT

Mycograb (
Neu
Tec Pharma plc) is a human genetically recombinant antibody against fungal heat shock protein 90 (HSP90). Antibody to HSP90 is closely associated with recovery in patients with invasive candidiasis who are receiving amphotericin B (AMB). Using in vitro assays developed for efficacy assessment of chemotherapeutic antifungal drugs, Mycograb showed activity against a wide range of yeast species (MICs against
Candida albicans
[fluconazole {FLC}-sensitive and FLC-resistant strains],
Candida krusei
,
Candida tropicalis
,
Candida glabrata
, and
Candida parapsilosis
, 128 to 256 μg/ml). Mycograb (4 or 8 μg/ml) showed synergy with AMB, the fractional inhibitory index being 0.09 to 0.31. Synergy was not evident with FLC, except for FLC-sensitive
C. albicans.
Murine kinetics showed that Mycograb at 2 mg/kg produced a maximum concentration of drug in serum of 4.7 μg/ml, a half-life at alpha phase of 3.75 min, a half-life at beta phase of 2.34 h, and an area under the concentration-time curve from 0 to
t
h of 155 μg · min/ml. Mycograb (2 mg/kg) alone produced significant improvement in murine candidiasis caused by each species: (i) a reduction (Scheffe's test,
P
< 0.05) in the mean organ colony count for the FLC-resistant strain of
C. albicans
(kidney, liver, and spleen),
C. krusei
(liver and spleen),
C. glabrata
(liver and spleen),
C. tropicalis
(kidney), and
C. parapsilosis
(kidney, liver, and spleen) and (ii) a statistically significant increase in the number of negative biopsy specimens (Fisher's exact test,
P
< 0.05) for
C. glabrata
(kidney),
C. tropicalis
(liver and spleen), and
C. parapsilosis
(liver). AMB (0.6 mg/kg) alone cleared the
C. tropicalis
infection but failed to clear infections caused by
C. albicans
,
C. krusei
,
C. glabrata
, or
C. parapsilosis.
Synergy with AMB, defined as an increase (Fisher's exact test,
P
< 0.05) in the number of negative biopsy specimens compared with those obtained using AMB alone, occurred with the FLC-resistant strain of
C. albicans
(kidney),
C. krusei
(spleen),
C. glabrata
(spleen), and
C. parapsilosis
(liver and spleen). Only by combining Mycograb with AMB was complete resolution of infection achieved for
C. albicans
,
C. krusei
, and
C. glabrata.