bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between E-Test, Disk Diffusion, and Microdilution Methods for Antifungal Susceptibility Testing of Fluconazole and Voriconazole
Authors: Matar Madonna J. , Ostrosky-Zeichner Luis , Paetznick Victor L. , Rodriguez Jose R. , Chen Enuo , Rex John H. 
Published: April 2003

ABSTRACT

The activities of fluconazole and voriconazole against isolates of
Candida
spp. (
n
= 400) were tested by the E-test, disk diffusion, and the National Committee for Clinical Laboratory Standards (NCCLS) M27-A2 broth microdilution-based reference methods. More than 96% of isolates found to be susceptible to fluconazole by the reference method were identified as susceptible by the agar-based methods. Lesser degrees of correlation with the reference method were seen for isolates identified as resistant by the agar-based methods. Interpretive categories are not available for voriconazole, but results qualitatively similar to those for fluconazole were seen. The agar-based E-test and disk diffusion methods are reliable alternatives to the NCCLS M27-A2 reference microdilution method for isolates that test susceptible to fluconazole.
In Vitro and In Vivo Activities of AM-112, a Novel Oxapenem
Authors: Jamieson Conor E. , Lambert Peter A. , Simpson Iain N. 
Published: April 2003

ABSTRACT

AM-112 [(1′R,5R,6R)-3-(4-amino-1,1-dimethyl-butyl)-6-(1′-hydroxyethyl)oxapenem-3-carboxylate] is a novel oxapenem compound which possesses potent β-lactamase-inhibitory properties. Fifty-percent inhibitory concentrations (IC
50
s) of AM-112 for class A enzymes were between 0.16 and 2.24 μM for three enzymes, compared to IC
50
s of 0.008 to 0.12 μM for clavulanic acid. Against class C and class D enzymes, however, the activity of AM-112 was between 1,000- and 100,000-fold greater than that of clavulanic acid. AM-112 had affinity for the penicillin-binding proteins (PBPs) of
Escherichia coli
DC0, with PBP2 being inhibited by the lowest concentration of AM-112 tested, 0.1 μg/ml. Ceftazidime was combined with AM-112 at 1:1 and 2:1 ratios in MIC determination studies against a panel of β-lactamase-producing organisms. These studies demonstrated that AM-112 was effective at protecting ceftazidime against extended-spectrum β-lactamase-producing strains and derepressed class C enzyme producers, reducing ceftazidime MICs by 16- and 2,048-fold. Similar results were obtained when AM-112 was combined with ceftriaxone, cefoperazone, or cefepime in a 1:2 ratio. Protection of ceftazidime with AM-112 was maintained against
Enterobacter cloacae
P99 and
Klebsiella pneumoniae
SHV-5 in a murine intraperitoneal sepsis model. The 50% effective dose of ceftazidime against
E. cloacae
P99 and
K. pneumoniae
SHV-5 was reduced from >100 and 160 mg/kg of body weight to 2 and 33.6 mg/kg, respectively, when it was combined with AM-112 at a 1:1 ratio. AM-112 demonstrates potential as a new β-lactamase inhibitor.
Molecular Evaluation of Antibiotic Susceptibility:
Tropheryma whipplei
Paradigm
Authors: Masselot F. , Boulos A. , Maurin M. , Rolain J. M. , Raoult D. 
Published: April 2003

ABSTRACT

Tropheryma whipplei
, the agent of Whipple's disease, grows fastidiously only in cell cultures without plaque production, and only three strains have been passaged. The formation of bacterial clumps in the supernatant precludes enumeration of viable bacteria and MIC determination. We evaluated the bacteriostatic effects of fluoroquinolones against two
T. whipplei
isolates by measuring the inhibition of the DNA copy number increase by real-time quantitative PCR. The analysis of the
T. whipplei
genome database allowed the identification not only of the
gyrA
gene but also the
parC
gene encoding the alpha subunit of the natural fluoroquinolone targets DNA gyrase (GyrA) and topoisomerase IV (ParC), respectively. The
parC
gene was detected in actinobacteria for the first time. High ciprofloxacin MICs (4 and 8 μg/ml) were correlated with the presence in
T. whipplei
GyrA and ParC sequences with an alanine residue at positions 83 and 80 (
Escherichia coli
numbering), respectively. Alanines at these positions have previously been associated with increased fluoroquinolone resistance in
E. coli
and mycobacteria. However, the MIC of levofloxacin was low (0.25 μg/ml). The same
T. whipplei
GyrA and ParC sequences were found in two other cultured strains and in nine uncultured tissue samples from Whipple's disease patients, allowing one to speculate that
T. whipplei
is naturally relatively resistant to fluoroquinolones.
Wolbachia pipientis
Growth Kinetics and Susceptibilities to 13 Antibiotics Determined by Immunofluorescence Staining and Real-Time PCR
Authors: Fenollar Florence , Maurin Max , Raoult Didier 
Published: April 2003

ABSTRACT

Wolbachia
spp. are strict intracellular bacteria that infect a wide range of arthropods and filarial nematodes. Filarial nematodes are important causes of human diseases. There is increasing evidence that
Wolbachia
spp. influence important functions in the biology of the hosts, specifically, infertility. Preliminary experiments with humans and animals have suggested that antibiotics with activity against
Wolbachia
may help to treat filariasis. In this study, we determined using a real-time quantitative PCR assay the growth kinetics of a strain of
Wolbachia pipientis
from a mosquito grown in Aa23 cells. The doubling time was estimated to be 14 h. We then determined the susceptibilities of this strain to 13 antibiotics by two methods: an immunofluorescent-antibody test and a real-time quantitative PCR assay. Both techniques gave similar results. Doxycycline and rifampin were the most effective compounds, with MICs of 0.125 and 0.06 to 0.125 μg/ml, respectively. Fluoroquinolones were less effective, with MICs of 2 to 4 μg/ml for ciprofloxacin, 2 μg/ml for ofloxacin, and 1 μg/ml for levofloxacin. β-Lactams (penicillin G, amoxicillin, ceftriaxone) were not effective at concentrations up to 128 μg/ml. The MIC of erythromycin was >32 μg/ml, whereas that of telithromycin was 8 μg/ml. Other antibiotic compounds were bacteriostatic only at high concentrations, including gentamicin, co-trimoxazole, and thiamphenicol. The real-time PCR assay was a convenient and reliable technique for determination of the antibiotic susceptibilities of
Wolbachia
. It may help in the future to simplify antibiotic susceptibility testing of strict intracellular pathogens.
Trends in Antimicrobial Susceptibilities among
Enterobacteriaceae
Isolated from Hospitalized Patients in the United States from 1998 to 2001
Authors: Karlowsky James A. , Jones Mark E. , Thornsberry Clyde , Friedland Ian R. , Sahm Daniel F. 
Published: April 2003

ABSTRACT

Longitudinal surveillance of
Enterobacteriaceae
for antimicrobial susceptibility is important because species of this family are among the most significant and prevalent human pathogens. To estimate rates of in vitro antimicrobial susceptibility among hospitalized patients in the United States, data from The Surveillance Network were studied for 14 agents tested against 10 species of
Enterobacteriaceae
(
n
= 384,279) isolated from intensive-care-unit (ICU) patients and non-ICU inpatients from 1998 to 2001. Cumulative susceptibility (percent) data for all species of
Enterobacteriaceae
isolated from ICU patients and non-ICU inpatients, respectively, were ranked as follows: ampicillin-sulbactam (45.5 and 57.2) ≪ ticarcillin-clavulanate (74.8 and 83.5) < trimethoprim-sulfamethoxazole (87.0 and 84.5) ≅ cefotaxime (82.9 and 92.6) = ceftazidime (82.3 and 91.0) = ceftriaxone (86.5 and 93.9) = piperacillin-tazobactam (83.5 and 90.5) < levofloxacin (89.3 and 90.6) = ciprofloxacin (91.0 and 91.7) < gentamicin (91.8 and 94.3) < cefepime (95.0 and 97.9) < amikacin (98.5 and 99.2) < imipenem (100 and 100) = meropenem (100 and 100). Of those agents studied only susceptibilities to ciprofloxacin (94 to 89%) and levofloxacin (93 to 89%) decreased in a stepwise manner from 1998 to 2001. Decreased fluoroquinolone susceptibility was most pronounced for
Escherichia coli
,
Proteus mirabilis
, and
Enterobacter cloacae
. For all species of
Enterobacteriaceae
, trimethoprim-sulfamethoxazole resistance was more commonly observed in isolates with a single-drug resistance phenotype while gentamicin and fluoroquinolone resistances were more common in isolates resistant to at least one additional class of antimicrobial agent. Ongoing surveillance of
Enterobacteriaceae
will be particularly important to monitor changes in fluoroquinolone susceptibility, as well as changes in the prevalence of isolates resistant to multiple classes of antimicrobial agents.
Surveillance for Antimicrobial Susceptibility among Clinical Isolates of
Pseudomonas aeruginosa
and
Acinetobacter baumannii
from Hospitalized Patients in the United States, 1998 to 2001
Authors: Karlowsky James A. , Draghi Deborah C. , Jones Mark E. , Thornsberry Clyde , Friedland Ian R. , Sahm Daniel F. 
Published: April 2003

ABSTRACT

Pseudomonas aeruginosa
and
Acinetobacter baumannii
are the most prevalent nonfermentative bacterial species isolated from clinical specimens of hospitalized patients. A surveillance study of 65 laboratories in the United States from 1998 to 2001 found >90% of isolates of
P
.
aeruginosa
from hospitalized patients to be susceptible to amikacin and piperacillin-tazobactam; 80 to 90% of isolates to be susceptible to cefepime, ceftazidime, imipenem, and meropenem; and 70 to 80% of isolates to be susceptible to ciprofloxacin, gentamicin, levofloxacin, and ticarcillin-clavulanate. From 1998 to 2001, decreases in antimicrobial susceptibility (percents) among non-intensive-care-unit (non-ICU) inpatients and ICU patients, respectively, were greatest for ciprofloxacin (6.1 and 6.5), levofloxacin (6.6 and 3.5), and ceftazidime (4.8 and 3.3). Combined 1998 to 2001 results for
A
.
baumannii
isolated from non-ICU inpatients and ICU patients, respectively, demonstrated that >90% of isolates tested were susceptible to imipenem (96.5 and 96.6%) and meropenem (91.6 and 91.7%); fewer isolates from both non-ICU inpatients and ICU patients were susceptible to amikacin and ticarcillin-clavulanate (70 to 80% susceptible); and <60% of isolates were susceptible to ceftazidime, ciprofloxacin, gentamicin, or levofloxacin. From 1998 to 2001, rates of multidrug resistance (resistance to at least three of the drugs ceftazidime, ciprofloxacin, gentamicin, and imipenem) showed small increases among
P
.
aeruginosa
strains isolated from non-ICU inpatients (5.5 to 7.0%) and ICU patients (7.4 to 9.1%). From 1998 to 2001, rates of multidrug resistance among
A
.
baumannii
strains isolated from non-ICU inpatients (27.6 to 32.5%) and ICU patients (11.6 to 24.2%) were higher and more variable than those observed for
P
.
aeruginosa
. Isolates concurrently susceptible, intermediate, or resistant to both imipenem and meropenem accounted for 89.8 and 91.2% of
P
.
aeruginosa
and
A
.
baumannii
isolates, respectively, studied from 1998 to 2001. In conclusion, for aminoglycosides and most β-lactams susceptibility rates for
P
.
aeruginosa
and
A
.
baumannii
were constant or decreased only marginally (≤3%) from 1998 to 2001. Greater decreases in susceptibility rates were, however, observed for fluoroquinolones and ceftazidime among
P
.
aeruginosa
isolates.
Baseline Study To Determine In Vitro Activities of Daptomycin against Gram-Positive Pathogens Isolated in the United States in 2000-2001
Authors: Critchley Ian A. , Blosser-Middleton Renée S. , Jones Mark E. , Thornsberry Clyde , Sahm Daniel F. , Karlowsky James A. 
Published: April 2003

ABSTRACT

The activity of daptomycin was assessed by using 6,973 gram-positive bacteria isolated at 50 United States hospitals in 2000 and 2001. Among the isolates of
Streptococcus pneumoniae
(
n
= 1,163) collected, the rate of penicillin resistance was 16.1%; rates of oxacillin resistance among
Staphylococcus aureus
isolates (
n
= 1,018) and vancomycin resistance among
Enterococcus faecium
isolates (
n
= 368) were 30.0 and 59.5%, respectively. Multidrug-resistant (MDR) phenotypes (isolates resistant to three or more different chemical classes of antimicrobial agents) accounted for 14.2% of
S. pneumoniae
isolates, 27.1% of
S. aureus
isolates, and 58.4% of
E. faecium
isolates. For all gram-positive species tested, MICs at which 90% of the isolates tested were inhibited (MIC
90
s) and MIC ranges for directed-spectrum agents (daptomycin, quinupristin-dalfopristin, and linezolid) were identical or highly similar for isolates susceptible or resistant to other agents or MDR. Daptomycin had a MIC
90
of 0.12 μg/ml for both penicillin-susceptible and -resistant isolates of
S. pneumoniae
. Against oxacillin-resistant
S. aureus
daptomycin had a MIC
90
of 0.5 μg/ml, and it had a MIC
90
of 4 μg/ml against both vancomycin-susceptible and -resistant
E. faecium
. The MIC
90
s for daptomycin and other directed-spectrum agents were unaffected by the regional or anatomical origin of isolates or patient demographic parameters (patient age, gender, and inpatient or outpatient care). Our results confirm the gram-positive spectrum of activity of daptomycin and that its activity is independent of susceptibility or resistance to commonly prescribed and tested antimicrobial agents. This study may serve as a baseline to monitor future changes in the susceptibility of gram-positive species to daptomycin following its introduction into clinical use.
Pharmacokinetics of Ritonavir and Delavirdine in Human Immunodeficiency Virus-Infected Patients
Authors: Shelton Mark J. , Hewitt Ross G. , Adams John , Della-Coletta Andrew , Cox Steven , Morse Gene D. 
Published: April 2003

ABSTRACT

To evaluate the pharmacokinetic effect of adding delavirdine mesylate to the antiretroviral regimens of human immunodeficiency virus (HIV)-infected patients stabilized on a full dosage of ritonavir (600 mg every 12 h), 12 HIV-1-infected subjects had delavirdine mesylate (400 mg every 8 h) added to their current antiretroviral regimens for 21 days. Ritonavir pharmacokinetics were evaluated before (day 7) and after (day 28) the addition of delavirdine, and delavirdine pharmacokinetics were evaluated on day 28. The mean values (± standard deviations) for the maximum concentration in serum (
C
max
) of ritonavir, the area under the concentration-time curve from 0 to 12 h (AUC
0-12
), and the minimum concentration in serum (
C
min
) of ritonavir before the addition of delavirdine were 14.8 ± 6.7 μM, 94 ± 36 μM · h, and 3.6 ± 2.1 μM, respectively. These same parameters were increased to 24.6 ± 13.9 μM, 154 ± 83 μM · h, and 6.52 ± 4.85 μM, respectively, after the addition of delavirdine (
P
is <0.05 for all comparisons). Delavirdine pharmacokinetic parameters in the presence of ritonavir included a
C
max
of 23 ± 16 μM, an AUC
0-8
of 114 ± 75 μM · h, and a
C
min
of 9.1 ± 7.5 μM. Therefore, delavirdine increases systemic exposure to ritonavir by 50 to 80% when the drugs are coadministered.
Pharmacodynamics of Oritavancin (LY333328) in a Neutropenic-Mouse Thigh Model of
Staphylococcus aureus
Infection
Authors: Boylan Carole J. , Campanale Kristina , Iversen Philip W. , Phillips Diane L. , Zeckel Michael L. , Parr Thomas R. 
Published: April 2003

ABSTRACT

The pharmacokinetics and pharmacodynamics of oritavancin (LY333328), a glycopeptide antibiotic with concentration-dependent bactericidal activity against gram-positive pathogens, in a neutropenic-mouse thigh model of
Staphylococcus aureus
infection were studied. Plasma radioequivalent concentrations of oritavancin were determined by using [
14
C]oritavancin at doses ranging from 0.5 to 20 mg/kg of body weight. Peak plasma radioequivalent concentrations after an intravenous dose were 7.27, 12.56, 69.29, and 228.83 μg/ml for doses of 0.5, 1, 5, and 20 mg/kg, respectively. The maximum concentration of drug in serum (
C
max
) and the area under the concentration-time curve (AUC) increased linearly in proportion to the dose. Neither infection nor neutropenia was seen to affect the pharmacokinetics of oritavancin. Intravenous administration resulted in much higher concentrations in plasma than the concentrations obtained with subcutaneous administration. Single-dose dose-ranging studies suggested a sigmoid maximum effect (
E
max
) dose-response relationship, with a maximal effect evident at single doses exceeding 2 mg/kg. The oritavancin dose (stasis dose) that resulted in a 24-h colony count similar to the pretreatment count was 1.53 (standard error [SE], 0.35) mg/kg. The single oritavancin dose that resulted in 50% of maximal bacterial killing (ED
50
) was 0.95 (SE, 0.20) mg/kg. Dose fractionation studies suggested that single doses of 0.5, 1, 2, 4, and 16 mg/kg appeared to have greater bactericidal efficacy than the same total dose subdivided and administered multiple times during the 24-h treatment period. When using an inhibitory
E
max
model,
C
max
appears to correlate better with bactericidal activity than do the time during which the concentration in plasma exceeds the MIC (T>MIC) and AUC. These data suggest that optimal oritavancin dosing strategies will require regimens that favor high
C
max
concentrations rather than long periods during which unbound concentrations in plasma exceed the MIC.
Differential Mutation Patterns in Thymidine Kinase and DNA Polymerase Genes of Herpes Simplex Virus Type 1 Clones Passaged in the Presence of Acyclovir or Penciclovir
Authors: Suzutani Tatsuo , Ishioka Ken , De Clercq Erik , Ishibashi Kei , Kaneko Hisatoshi , Kira Toshihiko , Hashimoto Koh-ichi , Ogasawara Masahiro , Ohtani Katsuki , Wakamiya Nobutaka , Saijo Masayuki 
Published: April 2003

ABSTRACTA total of 21 clones of acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) and 23 clones of penciclovir (PCV)-resistant (PCVr) HSV-1, emerging during serial passages in the presence of ACV or PCV, were isolated under conditions excluding contamination of resistant mutants in the starting virus culture, and their mutations in the thymidine kinase (TK) and DNA polymerase (DNA Pol) genes were analyzed comparatively. Mutations in the TK genes from ACVrmutants consisted of 50% single nucleotide substitutions and 50% frameshift mutations, while the corresponding figures for the PCVrmutants were 4 and 96%, respectively (P< 0.001). Eight of the 21 ACVrclones, but none of the 23 PCVrclones, had mutations in DNA Pol. Only nucleotide substitution(s) could be detected in the DNA Pol gene, as the gene is essential for virus replication. Therefore, the results for the DNA Pol mutants are concordant with those for the TK mutants in that a single nucleotide substitution was commonly observed in the ACVr, but not in the PCVr, mutants. These results clearly point to differential mutation patterns between ACVrand PCVrHSV-1 clones.
Efficacy of Daptomycin in Experimental Endocarditis Due to Methicillin-Resistant
Staphylococcus
aureus
Authors: Sakoulas George , Eliopoulos George M. , Alder Jeff , Eliopoulos Claudie Thauvin- 
Published: April 2003

ABSTRACT

Methicillin-resistant
Staphylococcus
aureus
is becoming increasingly prevalent as both a nosocomial and a community-acquired pathogen. Daptomycin, a lipopeptide antibiotic now in phase III clinical trials, is rapidly bactericidal in vitro against a range of gram-positive organisms, including methicillin-resistant
S. aureus
(MRSA). In this study, we compared the efficacy of daptomycin with that of vancomycin, each with or without rifampin, in a model of experimental aortic valve endocarditis due to MRSA. The infecting strain (MRSA strain 32) was susceptible to daptomycin (MIC = 1 μg/ml), vancomycin (MIC = 0.5 μg/ml), and rifampin (MIC = 0.5 μg/ml). Daptomycin was administered at 25 or 40 mg/kg q24h (q24h) by subcutaneous injection in an attempt to simulate human doses of 4 and 6 mg/kg q24h, respectively. Vancomycin was given at 150 mg/kg q24h by continuous intravenous infusion. Rifampin was given at 25 mg/kg by intramuscular injection q24h. Treatment was started 6 h postinoculation and continued for 4.5 days. Outcome was assessed by counting the residual viable bacteria in vegetations. The mean peak daptomycin levels in serum at 2 h after subcutaneous administration of 25 and 40 mg/kg were 64 and 91 μg/ml, respectively. Daptomycin was undetectable in serum at 24 h. The total exposure was comparable to that achieved clinically in humans receiving the drug. Bacterial counts (mean log
10
number of CFU per gram ± the standard deviation) in untreated controls reached 10.6 ± 0.8. In treated rats, bacterial counts were as follows: vancomycin, 7.1 ± 2.5; daptomycin at 25 mg/kg, 5.5 ± 1.7; daptomycin at 40 mg/kg, 4.2 ± 1.5. The difference between daptomycin at 40 mg/kg and vancomycin at 150 mg/kg was statistically significant (
P
= 0.004). In the study of combination therapy, vegetation bacterial counts were as follows: daptomycin at 40 mg/kg, 4.6 ± 1.6; rifampin, 3.6 ± 1.3; vancomycin plus rifampin, 3.3 ± 1.1; daptomycin plus rifampin, 2.9 ± 0.8. The difference between daptomycin and daptomycin plus rifampin was statistically significant (
P
= 0.006). These results support the continued evaluation of daptomycin for serious MRSA infections, including infective endocarditis.
Multiple Resistance Mechanisms among
Aspergillus fumigatus
Mutants with High-Level Resistance to Itraconazole
Authors: Nascimento Adriana M. , Goldman Gustavo H. , Park Steven , Marras Salvatore A. E. , Delmas Guillaume , Oza Uma , Lolans Karen , Dudley Michael N. , Mann Paul A. , Perlin David S. 
Published: April 2003

ABSTRACT

A collection of
Aspergillus fumigatus
mutants highly resistant to itraconazole (RIT) at 100 μg ml
−1
were selected in vitro (following UV irradiation as a preliminary step) to investigate mechanisms of drug resistance in this clinically important pathogen. Eight of the RIT mutants were found to have a mutation at Gly54 (G54E, -K, or -R) in the azole target gene
CYP51A
. Primers designed for highly conserved regions of multidrug resistance (MDR) pumps were used in reverse transcriptase PCR amplification reactions to identify novel genes encoding potential MDR efflux pumps in
A. fumigatus
. Two genes,
AfuMDR3
and
AfuMDR4
, showed prominent changes in expression levels in many RIT mutants and were characterized in more detail. Analysis of the deduced amino acid sequence encoded by
AfuMDR3
revealed high similarity to major facilitator superfamily transporters, while
AfuMDR4
was a typical member of the ATP-binding cassette superfamily. Real-time quantitative PCR with molecular beacon probes was used to assess expression levels of
AfuMDR3
and
AfuMDR4
. Most RIT mutants showed either constitutive high-level expression of both genes or induction of expression upon exposure to itraconazole. Our results suggest that overexpression of one or both of these newly identified drug efflux pump genes of
A. fumigatus
and/or selection of drug target site mutations are linked to high-level itraconazole resistance and are mechanistic considerations for the emergence of clinical resistance to itraconazole.