Abstract:
:There remains an unmet need to address the substantial morbidity and mortality associated with severe community-acquired pneumonia (sCAP). Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse animal models of infectious and noninfectious inflammation. This blinded dose-escalation safety study involved non-intensive care unit (ICU) patients admitted for mild CAP and randomized 3:1 to receive adjunctive rhu-pGSN or placebo intravenously. Thirty-three subjects were treated: 8 in the single-dose phase and 25 in the multidose phase. For the single-dose phase, rhu-pGSN at 6 mg/kg of body weight was administered once. For the multidose phase, a daily rhu-pGSN dose of 6, 12, or 24 mg/kg was given on 3 consecutive days. Adverse events (AEs) were generally mild in both treatment groups irrespective of dose. The only serious AE (SAE) in the single-dose phase was a non-drug-related pneumonia in a rhu-pGSN recipient who died after institution of comfort care. One single-dose placebo recipient had a drug-related AE (maculo-papular rash). In the multidose phase, there were 2 SAEs in 1 placebo recipient, including a fatal pulmonary embolism. In the 18 rhu-pGSN recipients in the multidose phase, there were no serious or drug-related AEs, and nausea and increased blood pressure were each reported in 2 patients. The median rhu-pGSN half-life exceeded 17 h with all dosing regimens, and supraphysiologic levels were maintained throughout the 24-h dosing interval in the 2 highest dosing arms. Rhu-pGSN was well tolerated overall in CAP patients admitted to non-ICU beds, justifying a larger proof-of-concept trial in an ICU population admitted with sCAP. (This study has been registered at ClinicalTrials.gov under identifier NCT03466073.).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Tannous A,Levinson SL,Bolognese J,Opal SM,DiNubile MJdoi
10.1128/AAC.00579-20subject
Has Abstractpub_date
2020-09-21 00:00:00issue
10eissn
0066-4804issn
1098-6596pii
AAC.00579-20journal_volume
64pub_type
杂志文章abstract::Conventional therapy for human cytomegalovirus (CMV) relies on inhibition of the viral DNA polymerase. Ganciclovir (GCV) is the first-line therapy, but when GCV-resistant strains emerge, alternative therapies are extremely limited and are associated with significant toxicities. Combination of anti-CMV agents that act ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01972-13
更新日期:2014-01-01 00:00:00
abstract::The potential for resistance development in Streptococcus pneumoniae secondary to exposure to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin at various levels was examined at high inoculum (10(8.5) to 10(9) log10 CFU/ml) over 96 h in an in vitro pharmacodynamic (PD) model using two fluoroquinolone-suscepti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00646-06
更新日期:2007-04-01 00:00:00
abstract::A gentamicin resistance determinant of a conjugative plasmid from Enterobacter cloacae was cloned on a 3.2-kilobase fragment in the PstI site of pBR322. Substrate profiles for eight aminoglycosides at three concentrations showed that the resistance was due to aminoglycoside-(3)-N-acetyltransferase isoenzyme II. Insert...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.8.1153
更新日期:1989-08-01 00:00:00
abstract::Caspofungin (CAS) is approved for second-line management of proven or probable invasive aspergillosis at a dose of 50 mg once daily (QD). Preclinical and limited clinical data support the concept of the dose-dependent antifungal efficacy of CAS with preservation of its favorable safety profile. Little is known, howeve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01912-12
更新日期:2013-04-01 00:00:00
abstract::Four large staphylococcal plasmids ranging in size from 31 to 82 kbp have been shown to mediate tetracycline resistance via an integrated copy of the tet(K)-encoding plasmid pT181 which was flanked by copies of the insertion element IS257. In two cases, IS257 elements interrupted the repC reading frame of pT181 and an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.11.2542
更新日期:1996-11-01 00:00:00
abstract::Ethambutol at 3.0 micrograms/ml inhibited the transfer of label from D-[14C]glucose into the D-arabinose residue of arabinogalactan in whole cells of a drug-susceptible strain of Mycobacterium smegmatis. This inhibition began almost immediately after exposure of the cells to the drug. When drug-resistant M. smegmatis ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1493
更新日期:1989-09-01 00:00:00
abstract::A total of 100 Streptococcus pneumoniae strains with various penicillin G susceptibilities, isolated in Barcelona, Spain, from different pediatric sources during 1983 and the first 4 months of 1984, were tested for susceptibility to tetracycline, chloramphenicol, erythromycin, clindamycin, vancomycin, and rifampin. Th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.2.357
更新日期:1985-08-01 00:00:00
abstract::Methionine gamma-lyase, the enzyme which catalyzes the single-step conversion of methionine to alpha-ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.6.1743-1745.2001
更新日期:2001-06-01 00:00:00
abstract::We have reported previously that methylenecyclopropane analogs of nucleosides have excellent activity against certain members of the herpesvirus family. A second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and 18 compounds were tested for activity in vitro against herpes simplex virus types 1 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.3.1039-1045.2005
更新日期:2005-03-01 00:00:00
abstract::A potential pharmacokinetic interaction between rifampin (Rimactan, Rifadin) and zidovudine (AZT, Retrovir) was investigated in the population of human immunodeficiency virus-infected patients at our hospital. The results from four patients who were on long-term (> or = 6 months) combination therapy with zidovudine an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.7.1426
更新日期:1993-07-01 00:00:00
abstract::Using measured free fraction and 50% inhibitory concentration (IC50) values for the human immunodeficiency virus protease inhibitors lopinavir (LPV) and ritonavir (RTV) in tissue culture media with various protein concentrations ranging from 5 to 50%, we estimated serum-free IC50 values for each drug. The range of ser...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.8.2911-2917.2004
更新日期:2004-08-01 00:00:00
abstract::Emtricitabine [(-)FTC] [(-)-beta-2', 3'-dideoxy-5-fluoro-3'-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (-)FTC against WHV rep...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1757-1760.2000
更新日期:2000-06-01 00:00:00
abstract::A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00378-19
更新日期:2019-06-24 00:00:00
abstract::The minimal inhibitory concentrations of 45 antimicrobial agents were determined for 14 strains of Bacterium actinomycetem comitans (Actinobacillus actinomycetem-comitans). All the strains showed good susceptibility to tetracyclines and chloramphenicol, but not to lincomycins. Some strains were clearly resistant to pe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.6.943
更新日期:1980-06-01 00:00:00
abstract::We have surveyed the susceptibility of 1,575 clinical isolates of the Bacteroides fragilis group of organisms to cefoxitin and eight other antimicrobial agents. Eleven isolates, 0.7% of the total, were highly cefoxitin resistant and had minimum inhibitory concentrations of greater than or equal to 64 micrograms/ml. Th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.6.936
更新日期:1983-12-01 00:00:00
abstract::The polyene antifungal amphotericin B (AmB) is widely used to treat life-threatening fungal infections. Even though AmB resistance is exceptionally rare in fungi, most Aspergillus terreus isolates exhibit an intrinsic resistance against the drug in vivo and in vitro. Heat shock proteins perform a fundamental protectiv...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05164-14
更新日期:2015-07-01 00:00:00
abstract::The therapeutic effectiveness of adenine arabinoside 5'-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AM...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.1.53
更新日期:1978-01-01 00:00:00
abstract::The enterococcal peptide AS-48 exerts a concentration-dependent bactericidal effect on Enterococcus faecalis subsp. liquefaciens S-47; cell rescue by cardiolipin and trypsin can be effected only in the first few minutes after antibiotic addition. Gramicidin-exposed cells are protected from killing by AS-48. Long-term ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.5.641
更新日期:1989-05-01 00:00:00
abstract::The bioavailabilities of orally administered drugs depend to a great extent on their capability of being transported across the intestinal mucosa. In an attempt to develop an in vitro model for studying the intestinal transport of drugs, we used an intestinal epithelial cell line (Caco 2) derived from a human colon ad...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.7.1374
更新日期:1992-07-01 00:00:00
abstract::As a relationship between nelfinavir antiretroviral efficacy and plasma concentrations has been previously established, nelfinavir pharmacokinetics was investigated in order to optimize the individual treatment schedule in a pediatric population. A population pharmacokinetic model was developed to describe the concent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.3.910-916.2006
更新日期:2006-03-01 00:00:00
abstract::We describe the clinical outcome of 17 patients with secondary Acinetobacter bacteremia whose isolates had a tigecycline MIC of ≤2 mg/liter and who received tigecycline within 2 days of bacteremia onset. The 14-day mortality rate of the tigecycline cohort was 41.2% (7/17), which was significantly higher than that of t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04987-14
更新日期:2015-01-01 00:00:00
abstract::The goal of the present study was to examine the ability of cytochrome P450-2C9 (CYP2C9) to activate cyclophosphamide (CPA) and elicit tumor cell death. A CYP2C9-deficient human lymphoblastoid cell line (AHH-1 cells) and a derivative cell line (H2C9 cells) stably transfected with a cDNA encoding CYP2C9 were used. The ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.10.2659-2663.2000
更新日期:2000-10-01 00:00:00
abstract::Ceftizoxime was evaluated in the treatment of 18 patients (6 adults and 12 children) with bacterial meningitis. In seven patients Haemophilus influenzae was the causative agent, in three Neisseria meningitidis, in five Streptococcus pneumoniae, and in one each alpha-streptococcus and Escherichia coli; one case was cul...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.2.258
更新日期:1984-02-01 00:00:00
abstract::Strains of Pseudomonas aeruginosa resistant to either gentamicin or carbenicillin have been noted since their introduction into clinical use. During a 6-month period, twice-weekly cultures were obtained from all patients treated with either gentamicin or carbenicillin and from all patients with a positive culture for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.3.474
更新日期:1976-03-01 00:00:00
abstract::The influence of reduced susceptibilities to glycopeptides on the activities of vancomycin and teicoplanin against an isogenic pair of clinical Staphylococcus aureus strains in experimental endocarditis was investigated. While vancomycin was similarly active against both strains, teicoplanin was approximately 100-fold...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.6.2018-2021.2003
更新日期:2003-06-01 00:00:00
abstract::Background antibiotic use (i.e., administration of antibiotics not directly related to Chlamydia trachomatis or Neisseria gonorrhoeae infections) has been associated with a lower prevalence of genital C. trachomatis infection in a clinical setting. Associations with specific antibiotic types or with N. gonorrhoeae are...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03932-14
更新日期:2015-01-01 00:00:00
abstract::The aim of this open-label, fixed-sequence study was to investigate the potential of the botanical supplement Echinacea purpurea to interact with etravirine, a nonnucleoside reverse transcriptase inhibitor of HIV. Fifteen HIV-infected patients receiving antiretroviral therapy with etravirine (400 mg once daily) for at...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.01205-12
更新日期:2012-10-01 00:00:00
abstract::The aim of this study was to investigate the influence of hypovolemia on the distribution of imipenem in muscle extracellular fluid determined by microdialysis in awake rats. Microdialysis probes were inserted into the jugular vein and hind leg muscle. Imipenem recoveries in muscle and blood were determined in each ra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.12.4974-4979.2005
更新日期:2005-12-01 00:00:00
abstract::Numerous bacterial pathogens, particularly those that colonize fast-flow areas in the bladder and gastrointestinal tract, require motility to establish infection and spread beyond the initially colonized tissue. Vibrio cholerae strains of serogroups O1 and O139, the causative agents of the diarrheal illness cholera, e...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00482-11
更新日期:2011-09-01 00:00:00
abstract::Omadacycline is an effective therapy for community-acquired bacterial pneumonia (CABP). Given its potent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA), we sought to determine the pharmacodynamic activity and target pharmacokinetic/pharmacodynamic (PK/P...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02058-19
更新日期:2020-01-27 00:00:00