bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidrug-Resistant
Salmonella enterica
Serovar Muenchen from Pigs and Humans and Potential Interserovar Transfer of Antimicrobial Resistance
Authors: Gebreyes Wondwossen A. , Thakur Siddhartha 
Published: January 2005

ABSTRACT

Salmonella
serovars are important reservoirs of antimicrobial resistance. Recently, we reported on multidrug-resistant (MDR)
Salmonella enterica
serovar Typhimurium strains among pigs with resistance to ampicillin, kanamycin, streptomycin, sulfamethoxazole, and tetracycline (resistance [R] type AKSSuT) and resistance to amoxicillin-clavulanic acid, ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (R type AxACSSuT). In the present study, 67 isolates (39 from humans and 28 from pigs) of clinically important
Salmonella
serovar Muenchen were characterized. Among the porcine isolates, 75% showed resistance to seven antimicrobials: ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline, amoxicillin-clavulanic acid, and kanamycin (R type ACSSuTAxK). One isolate from humans showed resistance to 10 of the 12 antimicrobials: ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline, amoxicillin-clavulanic acid, kanamycin, gentamicin, cephalothin, and ceftriaxone (R type ACSSuTAxKGCfCro). Pulsed-field gel electrophoresis revealed no clonality between the porcine and the human strains. The porcine and the human MDR strains carried class 1 integrons of 2.0 and 1.0 kb, respectively. Genes specific to the porcine strain included
aadA2
,
aphA1-Iab
, and
tetA
(B). DNA sequencing revealed that the porcine isolates carried
bla
OXA-30
on a class 1 integron. Genes specific to the human strain included
bla
TEM
,
strA
,
strB
,
cmlA
,
tetA
(A), and
aadA2
. No
bla
CMY-2
gene was detected. Serovar Muenchen strains of porcine and human origin were able to transfer resistance genes to laboratory strain
Escherichia coli
MG1655 by conjugation. Plasmid restriction with four restriction enzymes, EcoRI, BamHI, HindIII, and PstI, showed that the conjugative plasmids from porcine
Salmonella
serovar Muenchen and Typhimurium R-type MDR strains isolated from the same farms at the same time were similar on the basis of the sizes and the numbers of bands and Southern hybridization. The plasmid profiles among the
Salmonella
serovar Muenchen isolates from the two host species were different. This is the first report to show a high frequency of MDR
Salmonella
serovar Muenchen strains from pigs and a human strain that is similar to the MDR isolates with the AmpC enzyme previously reported among
Salmonella
serovars Newport and Typhimurium strains. The MDR strains from the two host species independently represent public health concerns, as
Salmonella
serovar Muenchen is among the top 10 causes of salmonellosis in humans.
Alkyl Gallates, Intensifiers of β-Lactam Susceptibility in Methicillin-ResistantStaphylococcus aureus
Authors: Shibata Hirofumi , Kondo Kyoko , Katsuyama Ryo , Kawazoe Kazuyoshi , Sato Yoichi , Murakami Kotaro , Takaishi Yoshihisa , Arakaki Naokatu , Higuti Tomihiko 
Published: January 2005

ABSTRACTWe found that ethyl gallate purified from a dried pod of tara (Caesalpinia spinosa) intensified β-lactam susceptibility in methicillin-resistant and methicillin-sensitive strains ofStaphylococcus aureus(MRSA and MSSA strains, respectively). This compound and several known alkyl gallates were tested with MRSA and MSSA strains to gain new insights into their structural functions in relation to antimicrobial and β-lactam susceptibility-intensifying activities. The maximum activity of alkyl gallates against MRSA and MSSA strains occurred at 1-nonyl and 1-decyl gallate, with an MIC at which 90% of the isolates tested were inhibited of 15.6 μg/ml. At concentrations lower than the MIC, alkyl gallates synergistically elevated the susceptibility of MRSA and MSSA strains to β-lactam antibiotics. Such a synergistic activity of the alkyl gallates appears to be specific for β-lactam antibiotics, because no significant changes were observed in the MICs of other classes of antibiotics examined in this study. The length of the alkyl chain was also associated with the modifying activity of the alkyl gallates, and the optimum length was C5 to C6. The present work clearly demonstrates that the length of the alkyl chain has a key role in the elevation of susceptibility to β-lactam antibiotics.
cDNA Microarray Analysis of Differential Gene Expression in
Candida albicans
Biofilm Exposed to Farnesol
Authors: Cao Ying-Ying , Cao Yong-Bing , Xu Zheng , Ying Kang , Li Yao , Xie Yi , Zhu Zhen-Yu , Chen Wan-Sheng , Jiang Yuan-Ying 
Published: January 2005

ABSTRACT

Candida albicans
biofilms are structured microbial communities with high levels of drug resistance. Farnesol, a quorum-sensing molecule that inhibits hyphal formation in
C. albicans
, has been found to prevent biofilm formation by
C. albicans
. There is limited information, however, about the molecular mechanism of farnesol against biofilm formation. We used cDNA microarray analysis to identify the changes in the gene expression profile of a
C. albicans
biofilm inhibited by farnesol. Confocal scanning laser microscopy was used to visualize and confirm normal and farnesol-inhibited biofilms. A total of 274 genes were identified as responsive, with 104 genes up-regulated and 170 genes down-regulated. Independent reverse transcription-PCR analysis was used to confirm the important changes detected by microarray analysis. In addition to hyphal formation-associated genes (e.g.,
TUP1
,
CRK1
, and
PDE2
), a number of other genes with roles related to drug resistance (e.g.,
FCR1
and
PDR16
), cell wall maintenance (e.g.,
CHT2
and
CHT3
), and iron transport (e.g.,
FTR2
) were responsive, as were several genes encoding heat shock proteins (e.g.,
HSP70
,
HSP90
,
HSP104
,
CaMSI3
, and
SSA2
). Further study of these differentially regulated genes is warranted to evaluate how they may be involved in
C. albicans
biofilm formation. Consistent with the down-regulation of the cell surface hydrophobicity-associated gene (
CSH1
), the water-hydrocarbon two-phase assay showed a decrease in cell surface hydrophobicity in the farnesol-treated group compared to that in the control group. Our data provide new insight into the molecular mechanism of farnesol against
C. albicans
biofilm formation.
Genotypic Characterization of the DNA Polymerase and Sensitivity to Antiviral Compounds of Foscarnet-Resistant Herpes Simplex Virus Type 1 (HSV-1) Derived from a Foscarnet-Sensitive HSV-1 Strain
Authors: Saijo Masayuki , Suzutani Tatsuo , Morikawa Shigeru , Kurane Ichiro 
Published: January 2005

ABSTRACTFoscarnet is widely used for the treatment of acyclovir-resistant herpesvirus infections, and foscarnet-resistant herpesvirus infections are a serious concern in immunocompromised patients. Twenty-seven single-plaque isolates of herpes simplex virus type 1 (HSV-1) resistant to foscarnet were selected from foscarnet- and acyclovir-sensitive HSV-1 strain TAS by exposure to foscarnet, and the DNA polymerase genes were analyzed. The sensitivities of these mutants to foscarnet, cidofovir, S2242, acyclovir, ganciclovir, and penciclovir were determined. A single amino acid substitution, double amino acid substitutions, and a combination of a single amino acid substitution with a deletion or insertion of amino acid residues in the viral DNA polymerase were demonstrated in 21, 4, and 2 isolates, respectively. Of the 27 isolates, an amino acid substitution of serine for asparagine at amino acid position 724 in the DNA polymerase (724 S-N) was detected in 8 isolates. An amino acid substitution in conserved region II was demonstrated in these eight isolates as well as four other isolates. The mutation in the DNA polymerase responsible for resistance to foscarnet was located between the pre-IV region and conserved region V, especially within conserved region II. All the isolates were sensitive or hypersensitive to cidofovir and ganciclovir. Seven, 5, and 15 of the 27 isolates were also sensitive to S2242, acyclovir, and penciclovir, respectively. Thus, most of the foscarnet-resistant HSV-1 isolates were sensitive or hypersensitive to cidofovir and ganciclovir.
Bactericidal Action of Gatifloxacin, Rifampin, and Isoniazid on Logarithmic- and Stationary-Phase Cultures of
Mycobacterium tuberculosis
Authors: Paramasivan C. N. , Sulochana S. , Kubendiran G. , Venkatesan P. , Mitchison D. A. 
Published: January 2005

ABSTRACT

The bactericidal activity of gatifloxacin, alone and in combination with isoniazid and rifampin, was studied on both exponential- and stationary-phase cultures of
Mycobacterium tuberculosis
strain H37Rv. On log-phase cultures, the bactericidal activity of gatifloxacin at 4 μg/ml was rapid and was very similar to that of isoniazid. At concentrations of 0.25 and 4 μg/ml, gatifloxacin enhanced the activity of isoniazid. Killing of the stationary-phase culture was biphasic. During the first 2 days, gatifloxacin at 4 μg/ml slightly increased the limited bactericidal activities of isoniazid and rifampin. However, no further additional bactericidal activity was found during further incubation with isoniazid alone or when gatifloxacin was added to either isoniazid or rifampin. This suggested that the stationary-phase culture contained a mixture of occasionally dividing bacilli that were killed during the first 2 days and true static persisters in the residual population that mimicked those in human lesions. In view of the failure of gatifloxacin to add to the sterilizing activity of isoniazid or rifampin during days 2 to 6 of exposure in the stationary-phase culture, it is unlikely to be a sterilizing drug that can be used to shorten the duration of treatment appreciably when it is added to present treatment regimens.
Interaction between Posaconazole and Amphotericin B in Concomitant Treatment against
Candida albicans
In Vivo
Authors: Cacciapuoti Anthony , Gurnani Maya , Halpern Judith , Norris Christine , Patel Reena , Loebenberg David 
Published: January 2005

ABSTRACT

The interaction of posaconazole and amphotericin B was evaluated in concomitant treatment of
Candida albicans
systemic infections in immunocompetent mice by using four strains of
C. albicans
with different susceptibilities to fluconazole. Posaconazole and amphotericin B were each tested at four dose levels alone and in all possible combinations against each
C. albicans
strain. Survival curves of mice treated with combinations of posaconazole and amphotericin B were statistically compared with those of mice treated with the component monotherapies. Of the 64 total combinations evaluated against the
C. albicans
strains (16 combinations per strain), 20.3% were more effective in prolonging mouse survival than both of the monotherapies, 45.3% were more effective than one of the monotherapies, and 32.8% were similar to both monotherapies. No evidence of antagonism was observed between posaconazole and amphotericin B in this mouse model, consistent with in vitro results against the same strains.
Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects
Authors: Regazzi Mario , Maserati Renato , Villani Paola , Cusato Maria , Zucchi Patrizia , Briganti Elena , Roda Rinaldo , Sacchelli Luca , Gatti Francesca , Delle Foglie Palma , Nardini Giulia , Fabris Paolo , Mori Fernanda , Castelli Paula , Testa Lucia 
Published: January 2005

ABSTRACT

In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV+) patients coinfected with HCV. A total of 119 HIV+ subjects were included in our study: 67 HIV+ patients, 32 HIV+ and HCV-positive (HCV+) patients without cirrhosis, and 20 HIV+ and HCV+ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day. To assay plasma NFV and M8 concentrations, patients underwent serial plasma samplings during the dosing interval at steady state. Plasma NFV and M8 concentrations were measured simultaneously by a high-performance liquid chromatography method with UV detection. The HIV+ and HCV+ patients with and without cirrhosis had significantly lower NFV oral clearances than the HIV+ and HCV-negative individuals (28 and 58% lower, respectively;
P
< 0.05), which translated into higher areas under the concentration-time curves for cirrhotic and noncirrhotic patients. The NFV absorption rate was significantly lower in cirrhotic patients, resulting in a longer time to the maximum concentration in serum. The mean ratios of the M8 concentration/NFV concentration were significantly lower (
P
< 0.05) in HIV+ and HCV+ subjects with cirrhosis (0.06 ± 0.074) than in the subjects in the other two groups. The mean ratios for M8 and NFV were not statistically different between HIV+ and HCV-negative patients (0.16 ± 0.13) and HIV+ and HCV+ patients without cirrhosis (0.24 ± 0.17), but the interpatient variability was high. Our results indicate that the pharmacokinetics of NFV and M8 are altered in HIV+ and HCV+ patients, especially those with liver cirrhosis. Therefore, there may be a role for therapeutic drug monitoring in individualizing the NFV dosage in HIV-HCV-coinfected patients.
Mefloquine versus Quinine plus Sulphalene-Pyrimethamine (Metakelfin) for Treatment of Uncomplicated Imported Falciparum Malaria Acquired in Africa
Authors: Matteelli Alberto , Saleri Nuccia , Bisoffi Zeno , Gregis Giampietro , Gaiera Giovanni , Visonà Raffaella , Tedoldi Simona , Scolari Carla , Marocco Stefania , Gulletta Maurizio 
Published: January 2005

ABSTRACT

We conducted a multicenter, randomized, open-label trial to compare mefloquine with a 3-day quinine plus sulphalene-pyrimethamine (SP) regimen for the treatment of imported uncomplicated malaria acquired in Africa. The end points of the study were efficacy, tolerability, and length of hospital stay. From July 1999 to February 2003, 187 patients were enrolled in five centers in Italy, of whom 93 were randomized to receive mefloquine (the M group) and 94 were randomized to receive quinine plus SP (the QSP group). Immigrants and visiting relatives and friends represented 90% of the cases and were mainly from western African countries. A slightly increased proportion of cases in the QSP group had abnormal alanine aminotransferase levels at the baseline. The early cure rate was similar in the two groups: 98.9% (confidence interval [CI] = 97 to 100%) in the M group and 96.8% (CI = 93 to 100%) in the QSP group. The extended follow-up was completed by 135 subjects (72.2%), and no case of recrudescence was detected. There were no differences in the parasite clearance time, but patients in the M group had shorter mean fever clearance time (35.9 h versus 44.4 h for the QSP group;
P
= 0.05) and a shorter mean hospital stay (3.9 days versus 4.6 days for the QSP group;
P
= 0.007). The overall proportions of reported side effects were similar in the two groups, but patients in the M group had a significantly higher rate of central nervous system disturbances (29.0% versus 9.6% for the QSP group;
P
< 0.001).
Mechanisms of Azole Resistance in Clinical Isolates of
Candida glabrata
Collected during a Hospital Survey of Antifungal Resistance
Authors: Sanguinetti Maurizio , Posteraro Brunella , Fiori Barbara , Ranno Stefania , Torelli Riccardo , Fadda Giovanni 
Published: January 2005

ABSTRACT

The increasing use of azole antifungals for the treatment of mucosal and systemic
Candida glabrata
infections has resulted in the selection and/or emergence of resistant strains. The main mechanisms of azole resistance include alterations in the
C. glabrata ERG11
gene (
CgERG11
), which encodes the azole target enzyme, and upregulation of the
CgCDR1
and
CgCDR2
genes, which encode efflux pumps. In the present study, we evaluated these molecular mechanisms in 29 unmatched clinical isolates of
C. glabrata
, of which 20 isolates were resistant and 9 were susceptible dose dependent (S-DD) to fluconazole. These isolates were recovered from separate patients during a 3-year hospital survey for antifungal resistance. Four of the 20 fluconazole-resistant isolates were analyzed together with matched susceptible isolates previously taken from the same patients. Twenty other azole-susceptible clinical
C. glabrata
isolates were included as controls. MIC data for all the fluconazole-resistant isolates revealed extensive cross-resistance to the other azoles tested, i.e., itraconazole, ketoconazole, and voriconazole. Quantitative real-time PCR analyses showed that
CgCDR1
and
CgCDR2
, alone or in combination, were upregulated at high levels in all but two fluconazole-resistant isolates and, to a lesser extent, in the fluconazole-S-DD isolates. In addition, slight increases in the relative level of expression of
CgSNQ2
(which encodes an ATP-binding cassette [ABC] transporter and which has not yet been shown to be associated with azole resistance) were seen in some of the 29 isolates studied. Interestingly, the two fluconazole-resistant isolates expressing normal levels of
CgCDR1
and
CgCDR2
exhibited increased levels of expression of
CgSNQ2
. Conversely, sequencing of
CgERG11
and analysis of its expression showed no mutation or upregulation in any
C. glabrata
isolate, suggesting that
CgERG11
is not involved in azole resistance. When the isolates were grown in the presence of fluconazole, the profiles of expression of all genes, including
CgERG11
, were not changed or were only minimally changed in the resistant isolates, whereas marked increases in the levels of gene expression, particularly for
CgCDR1
and
CgCDR2
, were observed in either the fluconazole-susceptible or the fluconazole-S-DD isolates. Finally, known ABC transporter inhibitors, such as FK506, were able to reverse the azole resistance of all the isolates. Together, these results provide evidence that the upregulation of the
CgCDR1
-,
CgCDR2
-, and
CgSNQ2
-encoded efflux pumps might explain the azole resistance in our set of isolates.
Pharmacokinetic Study of Tenofovir Disoproxil Fumarate Combined with Rifampin in Healthy Volunteers
Authors: Droste J. A. H. , Verweij-van Wissen C. P. W. G. M. , Kearney B. P. , Buffels R. , vanHorssen P. J. , Hekster Y. A. , Burger D. M. 
Published: January 2005

ABSTRACT

Tenofovir disoproxil fumarate (tenofovir DF) was studied in combination with rifampin in 24 healthy subjects in a multiple-dose, open-label, single-group, two-period study. All subjects were given tenofovir DF at 300 mg once a day (QD) from days 1 to 10 (period 1). From days 11 to 20 the subjects received tenofovir DF at 300 mg combined with rifampin at 600 mg QD (period 2). The multiple-dose pharmacokinetics of tenofovir (day 10 and 20) and rifampin (day 20) were assessed. The drug-related adverse events (AEs) experienced during this study were mostly mild. Only one grade 3 AE possibly or probably related to the treatment (raised liver enzyme levels) occurred during period 2; the subject was withdrawn from the study. Pharmacokinetic data for 23 subjects were thus evaluable. Point estimates for the mean ratios of tenofovir with rifampin versus tenofovir alone for the area under the concentration-time curve from time zero to 24 h (AUC
0-24
), the maximum concentration of drug in plasma (
C
max
), and the minimum concentration of drug in plasma (
C
min
) were 0.88, 0.84, and 0.85, respectively. The 90% classical confidence intervals for AUC
0-24
,
C
max
, and
C
min
were 0.84 to 0.92, 0.78 to 0.90, and 0.80 to 0.91, respectively, thus suggesting pharmacokinetic equivalence. Similarly, coadministration of rifampin and tenofovir DF did not result in changes in the values of the tenofovir pharmacokinetic parameters. For rifampin, the values of the pharmacokinetic parameters found in this study were comparable to those found in the literature, indicating that tenofovir DF has no effect on the pharmacokinetics of rifampin. In conclusion, adaptation of either the rifampin or the tenofovir DF dose for the simultaneous treatment of tuberculosis and human immunodeficiency virus (HIV) infection in HIV-infected patients is probably not required.
Levofloxacin plus Metronidazole Administered Once Daily versus Moxifloxacin Monotherapy against a Mixed Infection of
Escherichia coli
and
Bacteroides fragilis
in an In Vitro Pharmacodynamic Model
Authors: Hermsen Elizabeth D. , Hovde Laurie B. , Sprandel Kelly A. , Rodvold Keith A. , Rotschafer John C. 
Published: January 2005

ABSTRACT

Moxifloxacin has been suggested as an option for monotherapy of intra-abdominal infections. Recent data support the use of a once-daily metronidazole regimen. The purpose of this study was to investigate the activity of levofloxacin (750 mg every 24 h [q24h]) plus metronidazole (1,500 mg q24h) compared with that of moxifloxacin (400 mg q24h) monotherapy in a mixed-infection model. By using an in vitro pharmacodynamic model in duplicate,
Escherichia coli
and
Bacteroides fragilis
were exposed to peak concentrations of 8.5 mg of levofloxacin/liter q24h, 32 mg of metronidazole/liter q24h, and 2 mg for moxifloxacin/liter q24h for 24 h. The activities of levofloxacin, metronidazole, moxifloxacin, and levofloxacin plus metronidazole were evaluated against
E. coli
,
B. fragilis
, and
E. coli
plus
B. fragilis
. The targeted half-lives of levofloxacin, metronidazole, and moxifloxacin were 8, 8, and 12 h, respectively. Time-kill curves were analyzed for time to 3-log killing, slope, and regrowth. Pre- and postexposure MICs were determined. The preexposure levofloxacin, metronidazole, and moxifloxacin MICs for
E. coli
and
B. fragilis
were 0.5 and 1, >64 and 0.5, and 1 and 0.25 mg/liter, respectively. Levofloxacin and moxifloxacin achieved a 3-log killing against
E. coli
and
B. fragilis
in all experiments, as did metronidazole against
B. fragilis
. Metronidazole did not decrease the starting inoculum of
E. coli
. The area under the concentration-time curve/MIC ratios for
E. coli
and
B. fragilis
were 171.7 and 85.9, respectively, for levofloxacin and 26 and 103.9, respectively, for moxifloxacin. Levofloxacin plus metronidazole exhibited the fastest rates of killing. The levofloxacin and moxifloxacin MICs for
B. fragilis
increased 8- to 16-fold after the organism was exposed to moxifloxacin. No other changes in the postexposure MICs were found. Levofloxacin plus metronidazole administered once daily exhibited activity similar to that of moxifloxacin against the mixed
E. coli
and
B. fragilis
infection. A once-daily regimen of levofloxacin plus metronidazole looks promising for the treatment of intra-abdominal infections.