Abstract:
:The aim of this study was to investigate the variability of the voriconazole plasma level and its relationships with clinical outcomes and adverse events among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included, and voriconazole trough levels were quantified by a validated high-performance liquid chromatography method. Cytochrome P450 genotypes for CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured. Proven, probable, and possible invasive fungal infections were reported for 8/104 (7.7%), 42/104 (40.4%), and 54/104 (51.9%) patients, respectively. Receiver operating characteristic (ROC) curve analysis indicated that trough concentrations of ≥1.3 μg/ml minimized the incidence of treatment failure (95% confidence interval [CI], 0.68 to 0.91 μg/ml) (P < 0.001) and that those of <5.3 μg/ml minimized the incidence of any adverse events (95% CI, 0.83 to 0.97 μg/ml) (P < 0.001). Voriconazole trough levels were significantly higher for heterozygous extensive metabolizers, poor metabolizers, and individuals receiving coadministration with proton pump inhibitors. For ultrarapid metabolizers, oral administration of voriconazole, and concomitant use of glucocorticoids, voriconazole blood concentrations were significantly reduced. Furthermore, there was no statistically significant association of patient age, weight, or gender or coadministration of tacrolimus and cyclosporine with the voriconazole trough level. In conclusion, the results of our analysis indicate large inter- and intraindividual variabilities of voriconazole concentrations in liver transplant recipients. Voriconazole trough concentrations of ≥1.3 μg/ml and <5.3 μg/ml are optimal for treatment and for minimization of adverse events. Optimization of drug efficacy and safety requires the use of rational doses for voriconazole therapy.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Hashemizadeh Z,Badiee P,Malekhoseini SA,Raeisi Shahraki H,Geramizadeh B,Montaseri Hdoi
10.1128/AAC.01211-17subject
Has Abstractpub_date
2017-11-22 00:00:00issue
12eissn
0066-4804issn
1098-6596pii
AAC.01211-17journal_volume
61pub_type
杂志文章abstract::Receipt of parenteral nutrition (PN) remains an independent risk factor for developing catheter-related bloodstream infections (CR-BSI) caused by fungi, including by the polymorphic fungus Candida albicans, which is notoriously adept at forming drug-resistant biofilm structures. Among a variety of macronutrients, PN s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01394-19
更新日期:2019-10-22 00:00:00
abstract::We developed a multiplex real-time SYBR green-based PCR assay for rapid detection of tet(X) and its variants, including tet(X1) and tet(X2) and high-level tigecycline resistance genes tet(X3), tet(X4), and tet(X5). We showed that the real-time PCR assay developed had high linearity (R2 ≥ 0.996), sensitivity (low detec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02292-19
更新日期:2020-03-24 00:00:00
abstract::Multidrug resistance in Gram-negative bacteria has become so threatening to human health that new antibacterial platforms are desperately needed to combat these deadly infections. The concept of siderophore conjugation, which facilitates compound uptake across the outer membrane by hijacking bacterial iron acquisition...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00629-13
更新日期:2013-09-01 00:00:00
abstract::The long-term cumulative cytotoxicity of antiretrovirals (ARVs) is among the major causes of treatment failure in patients infected with human immunodeficiency virus (HIV) and patients with AIDS. This calls for the development of novel ARVs with less or no cytotoxicity. In the present study, we compared the cytotoxic ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01502-08
更新日期:2009-07-01 00:00:00
abstract::Triple antifungal combinations are used against refractory invasive aspergillosis without an adequate understanding of their pharmacodynamic interactions. We initially studied the in vitro triple combination of voriconazole, amphotericin B, and caspofungin against Aspergillus fumigatus, A. flavus, and A. terreus by a ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00873-06
更新日期:2007-06-01 00:00:00
abstract::The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approxim...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/AAC.48.6.2061-2068.2004
更新日期:2004-06-01 00:00:00
abstract::Pseudomonas aeruginosa is equipped with the Sec and Tat protein secretion systems, which translocate the xenobiotic transporter MexAB-OprM and the pathogenic factor phospholipase C (PlcH), respectively. When the signal sequence of MexA was replaced with that of PlcH, the hybrid protein was successfully expressed and r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01495-09
更新日期:2010-04-01 00:00:00
abstract::Protozoan parasites of the Leishmania donovani complex are the causative agents of visceral leishmaniasis (VL), the most severe form of leishmaniasis, with high rates of mortality if left untreated. Leishmania parasites are transmitted to humans through the bite of infected female sandflies (Diptera: Phlebotominae), a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00478-16
更新日期:2016-06-20 00:00:00
abstract::Currently, CTX-M β-lactamases are among the most prevalent and most heterogeneous extended-spectrum β-lactamases (ESBLs). In general, CTX-M enzymes are susceptible to inhibition by β-lactamase inhibitors. However, it is unknown if the pathway to inhibition by β-lactamase inhibitors for CTX-M ESBLs is similar to TEM an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00089-11
更新日期:2011-07-01 00:00:00
abstract::Occidiofungin is a cyclic glyco-lipopeptide produced by Burkholderia contaminans. MICs against Candida species were between 0.5 and 2.0 μg/ml. Occidiofungin retains its in vitro potency in the presence of 5% and 50% human serum with a minimal lethal concentration (MLC) of 2 and 4 μg/ml, respectively. Time-kill and pos...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05231-11
更新日期:2012-02-01 00:00:00
abstract::Plasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03337-14
更新日期:2014-12-01 00:00:00
abstract::Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02109-15
更新日期:2016-03-25 00:00:00
abstract::Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that are efficacious against major drivers of influenza-like disease, including influenza viruses and respiratory syncytial virus (R...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00766-18
更新日期:2018-07-27 00:00:00
abstract::A novel plasmid-borne resistance gene cluster comprising the genes erm(T) for macrolide-lincosamide-streptogramin B resistance, dfrK for trimethoprim resistance, and tet(L) for tetracycline resistance was identified in a porcine methicillin-resistant Staphylococcus aureus sequence type 398 (ST398) strain. This erm(T)-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01091-09
更新日期:2010-02-01 00:00:00
abstract::Mecillinam is an amidino penicillinate derivative with a broad spectrum of activity against many gram-negative bacilli. Moreover, marked in vitro synergy against these organisms occurs when mecillinam is combined with other beta-lactam antibiotics. The purpose of this study was to determine the pharmacokinetic disposi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.6.952
更新日期:1980-12-01 00:00:00
abstract::A 7.7-kilobase BamHI fragment was cloned from the transconjugant of a clinical isolate of Escherichia coli containing a 120-kilobase multiresistance IncC plasmid. The recombinant plasmid conferred resistance to kanamycin, gentamicin, tobramycin, sulfamethoxazole, and trimethoprim. This clone was used to generate a ser...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.1.96
更新日期:1985-07-01 00:00:00
abstract::Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts through inhibition of a P-450 enzyme undertaking sterol 14alpha demethylation. In vitro resistance in Aspergillus fumig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.6.1364
更新日期:1997-06-01 00:00:00
abstract::Pseudomonas aeruginosa is a multidrug-resistant nosocomial pathogen. We showed previously that thiostrepton (TS), a Gram-positive thiopeptide antibiotic, is imported via pyoverdine receptors and synergizes with iron chelator deferasirox (DSX) to inhibit the growth of P. aeruginosa and Acinetobacter baumannii clinical ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01909-19
更新日期:2020-02-21 00:00:00
abstract::An Escherichia coli strain with a plasmidic amikacin resistance has been selected for which the evidence strongly indicates that resistance is mediated by aminoglycoside phosphotransferase [APH(3')-II]: (i) this resistance was coupled with resistance against kanamycin and neomycin; (ii) partially purified APH(3')-II[A...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.344
更新日期:1981-09-01 00:00:00
abstract::Increasingly frequent reports have described the in vivo loss of daptomycin susceptibility in association with clinical treatment failures. The mechanism(s) of daptomycin resistance is not well understood. We studied an isogenic set of Staphylococcus aureus isolates from the bloodstream of a daptomycin-treated patient...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00719-07
更新日期:2008-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01745-16
更新日期:2017-01-24 00:00:00
abstract::The need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their poten...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00639-13
更新日期:2013-09-01 00:00:00
abstract::In a previous work, we described the possible relationship between a defect of purine-cytosine permease and the acquisition of a cross-resistance to the antifungal combination flucytosine (5FC) and fluconazole (FLC) in Candida lusitaniae (T. Noël, F. François, P. Paumard, C. Chastin, D. Brethes, and J. Villard, Antimi...
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doi:10.1128/AAC.49.8.3101-3108.2005
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abstract::Gatifloxacin pneumococcal, staphylococcal and enterococcal postantibiotic effects (PAEs) were 0.5 to 4.0 h, respectively. For Escherichia coli and Pseudomonas aeruginosa, PAEs were 2.2 to 4.8 h. Pneumococcal, staphylococcal, and enterococcal postantibiotic sub-MIC effects (PA-SMEs) (four times the MICs) were 3.7 to 8....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.10.2574
更新日期:1999-10-01 00:00:00
abstract::Topical foscarnet (PFA) and acyclovir (ACV) were compared in the dorsal cutaneous guinea pig model of herpes simplex virus type 1 infection. The relative order of efficacy was PFA cream greater than ACV cream greater than ACV ointment. In vitro studies demonstrated that PFA and ACV formulated in cream vehicles penetra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.1.196
更新日期:1986-07-01 00:00:00
abstract::Loss of viability of toxin-treated cells of Saccharomyces cerevisiae SCF 1717 could be prevented in the period before they altered physiologically if cells were incubated in media with a suitable concentration of potassium (0.08 to 0.13 M) and hydrogen ions (pH 6.2 to 6.7). Incorporation of higher amounts of potassium...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.4.519
更新日期:1980-10-01 00:00:00
abstract::Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00440-20
更新日期:2020-04-21 00:00:00
abstract::Induction of the cloned ampC Citrobacter freundii beta-lactamase in Escherichia coli by 6-aminopenicillanic acid was prevented by periplasmic TEM beta-lactamase in the same cell. In contrast, cytoplasmic TEM beta-lactamase did not prevent induction. This result implies that entry of the beta-lactam into the cytoplasm ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.12.2429
更新日期:1990-12-01 00:00:00
abstract::The increasing resistance of human pathogens to conventional antibiotics presents a growing threat to the chemotherapeutic management of infectious diseases. The lanthionine antibiotics, still unused as therapeutic agents, have recently attracted significant scientific interest as models for targeting and management o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00836-07
更新日期:2008-02-01 00:00:00
abstract::Multilocus microsatellite polymorphisms in 27 clinical Candida albicans isolates were found to be clearly unrelated to in vitro paradoxical growth or trailing effect with caspofungin. These findings suggest that such in vitro phenotypes are either gained or lost too rapidly to be predicted by more stable genomic marke...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00530-09
更新日期:2010-03-01 00:00:00