Abstract:
:Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen associated with nosocomial pneumonia and is an increasing threat for severe community-acquired pneumonia. We have now investigated the role of interleukin-12 (IL-12) in protective immunity against lung infection with MRSA. The importance of IL-12 in protection from pulmonary MRSA infection was demonstrated by the finding that IL-12p35-deficient mice had a lower survival rate, higher bacterial burdens in lung and spleen, and decreased expression of interferon gamma (IFN-γ) in the lung compared to wild-type mice. These effects were completely reversed by replacement intranasal therapy with recombinant IL-12. Furthermore, exogenous IL-12 treatment of wild-type mice 24 h before pulmonary challenge with a lethal dose of MRSA significantly improved bacterial clearance and resulted in protection from death. The IL-12-treated mice had increased numbers of lung natural killer (NK) cells and neutrophils and higher levels of IFN-γ in the lung and serum compared to untreated mice. The major source of IL-12-driven IFN-γ expression in the lung was the NK cell, and the direct target of pulmonary IFN-γ was the lung macrophage, as shown using mice with a macrophage-specific defect in interferon gamma (IFN-γ) signaling (MIIG mice). Importantly, combination therapy with linezolid and IL-12 following intranasal MRSA infection significantly increased survival compared to that of mice receiving linezolid or IL-12 alone. These results indicate that IL-12-based immunotherapy may hold promise for treatment of MRSA pneumonia.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Nguyen QT,Furuya Y,Roberts S,Metzger DWdoi
10.1128/AAC.00968-15subject
Has Abstractpub_date
2015-10-01 00:00:00pages
6308-16issue
10eissn
0066-4804issn
1098-6596pii
AAC.00968-15journal_volume
59pub_type
杂志文章abstract::The pharmacokinetics of cefmenoxime were characterized in five healthy volunteers and in 15 subjects with various degrees of renal insufficiency after a single 10-mg/kg, 5-min intravenous infusion. Five of these subjects were studied both on hemodialysis and during an interdialytic period. Plasma, urine and dialysate ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.6.845
更新日期:1984-12-01 00:00:00
abstract::The anti-human immunodeficiency virus type I (anti-HIV-1) effects of gamma-glutamylcysteine ethyl ester (gamma-GCE; TEI-2306) were examined in vitro. In initial studies using a vigorously HIV-1-producing human T-lymphocytic cell line, gamma-GCE displayed a novel biphasic repressive effect on chronic HIV-1 infection th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.5.1200
更新日期:1998-05-01 00:00:00
abstract::Beta-l-2',3'-didehydro-2',3'-dideoxy-N(4)-hydroxycytidine (l-Hyd4C) was demonstrated to be an effective and highly selective inhibitor of hepatitis B virus (HBV) replication in HepG2.2.15 cells (50% effective dose [ED(50)] = 0.03 microM; 50% cytotoxic dose [CD(50)] = 2,500 microM). In the present study, we investigate...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01176-09
更新日期:2010-01-01 00:00:00
abstract::Two new antifungal triazoles, BAY n7133 and ICI 153,066, were compared with ketoconazole in treatment of mice challenged intraperitoneally with Cryptococcus neoformans. At high challenge doses, thymus-containing normal mice had prolonged survival after treatment with BAY n7133. Athymic mice, which have severely defici...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.6.829
更新日期:1983-12-01 00:00:00
abstract::An increase in the number of tuberculosis cases caused by multiple-drug-resistant strains of Mycobacterium tuberculosis has stimulated search for new antituberculous agents. Beta-lactam antibiotics, traditionally regarded as ineffective against tuberculosis, merit consideration. Four major penicillin-binding proteins ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.12.2620
更新日期:1995-12-01 00:00:00
abstract::Iron-sulfur flavoproteins (Isf) are flavin mononucleotide (FMN)- and FeS cluster-containing proteins commonly encountered in anaerobic prokaryotes. However, with the exception of Isf from Methanosarcina thermophila, which participates in oxidative stress management by removing oxygen and hydrogen peroxide, none of the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02320-13
更新日期:2014-06-01 00:00:00
abstract::We performed the characterization of a multidrug-resistant (MDR) Enterobacter spp. isolate highlighting the genetic aspects of the antimicrobial resistance genes. An Enterobacter spp. isolate (Ec61) was recovered in 2014 from a transtracheal aspirate sample from a patient admitted to a Brazilian tertiary hospital and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01193-20
更新日期:2020-12-14 00:00:00
abstract::Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents. Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.10.2431
更新日期:1996-10-01 00:00:00
abstract::Fifty-seven cultures of Haemophilus influenzae were tested for production of beta-lactamase by use of a modified, 1-min test. Only the 24 cultures that were ampicillin resistant, whether type b or not, yielded positive results for the enzyme; all ampicillin-susceptible isolates were uniformly negative. The beta-lactam...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.1.196
更新日期:1976-01-01 00:00:00
abstract::Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia. Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial with adult patients presenting with acute fe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1128/AAC.00508-07
更新日期:2007-09-01 00:00:00
abstract::GES-1 is a class A extended-spectrum β-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins and exhibits very low k(cat) values for carbapenems. Twenty-two GES variants have been discovered thus far, di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01272-12
更新日期:2012-11-01 00:00:00
abstract::A patient with AIDS and chronic diarrhea caused by Enterocytozoon bieneusi was successfully treated with nitazoxanide, producing a complete clinical and parasitological response, while off of antiviral therapy. This suggests that nitazoxanide may be effective in treating microsporidiosis caused by E. bieneusi, a disea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.1.167-168.2000
更新日期:2000-01-01 00:00:00
abstract::Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.2.161
更新日期:1979-02-01 00:00:00
abstract::Drug exposure or pharmacodynamic breakpoints refer to a magnitude of drug exposure which separates a population into groups with high and low probabilities of attaining a desired outcome. We used a pharmacodynamic model of disseminated candidiasis to define an in vivo drug exposure breakpoint for flucytosine (5FC) aga...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00369-06
更新日期:2006-11-01 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::Methicillin-resistant Staphylococcus aureus (MRSA) has become a significant acute and chronic respiratory pathogen. While vancomycin is effective against MRSA, its relatively poor penetration into lung secretions and dose-limiting renal toxicity make it less effective in the respiratory setting. As inhaled administrat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01776-19
更新日期:2020-02-21 00:00:00
abstract::Trimethoprim resistance dihydrofolate reductase genes from plasmids known to be exchanging between human and animal populations were mapped. The dihydrofolate reductase gene has been highly conserved in all plasmids, but differences in the flanking regions provide evidence that the most recent exchange of plasmids bet...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.9.1440
更新日期:1987-09-01 00:00:00
abstract::The VanR-VanS two-component system is responsible for inducing resistance to glycopeptide antibiotics in various bacteria. We have performed a comparative study of the VanR-VanS systems from two streptomyces strains, Streptomyces coelicolor and Streptomyces toyocaensis, to characterize how the two proteins cooperate t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01367-15
更新日期:2015-12-28 00:00:00
abstract::Drug susceptibility tests (DSTs) for Mycobacterium tuberculosis require at least 7 days of incubation. Drugs that are unstable at 37°C, such as ertapenem, are likely to be degraded before killing or inhibiting slow-growing bacteria. This would alter the MICs of these drugs, including ertapenem, leading to falsely high...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02924-15
更新日期:2016-04-22 00:00:00
abstract::We undertook this study to investigate whether treatment with a higher dose of trimethoprim-sulfamethoxazole (TMP/SMX) led to greater clinical resolution in patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). A prospective, observational cohort with neste...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.00706-11
更新日期:2011-12-01 00:00:00
abstract::Teicoplanin was evaluated in 47 patients with severe infections, including 14 patients with bone infections, 11 patients with soft-tissue infections, 7 patients with endocarditis, 5 patients with pneumonia, 3 patients with septic thrombophlebitis, 3 patients with septicemia of unknown origin, and 4 patients with misce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.1.52
更新日期:1986-01-01 00:00:00
abstract::Invasive pulmonary aspergillosis (IPA) continues to rise in concert with increasing numbers of immune suppression techniques to treat other medical conditions and transplantation. Despite these advances, morbidity and mortality rates remain unacceptably high. One strategy used to optimize outcomes is antifungal pharma...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01355-13
更新日期:2013-12-01 00:00:00
abstract::Amoxicillin and ampicillin were compared at a dose of 250 mg twice daily for 4 weeks to treat Salmonella typhi or Salmonella paratyphi A chronic bacteriuria with intermittent bacteremia. Eleven patients received amoxicillin, and 15 received ampicillin. Concentrations of the two drugs were measured in the urine and ser...
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.20.5.630
更新日期:1981-11-01 00:00:00
abstract::We assessed prophylactic or continuous therapy of isavuconazole, posaconazole, or voriconazole in treating pulmonary murine mucormycosis. In the prophylaxis studies, only isavuconazole treatment resulted in significantly improved survival and lowered tissue fungal burden of immunosuppressed mice infected with Rhizopus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02589-16
更新日期:2017-04-24 00:00:00
abstract::Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01009-20
更新日期:2020-12-16 00:00:00
abstract::Yersinia enterocolitica has emerged as an enteropathogen associated with several types of human infections that often require antimicrobial therapy, but little is known about the antimicrobial susceptibilities of pathogenic strains isolated from humans in Canada. To determine the present patterns of antimicrobial susc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2121
更新日期:1994-09-01 00:00:00
abstract::Nine intubated patients were given a single, 2-g intravenous dose of aztreonam over 5 min. Samples of serum and bronchial secretion were obtained 2, 4, and 8 h after administration and assayed for aztreonam content. The mean concentrations in bronchial secretion ranged from 1.9 to 5.2 micrograms/ml and tended to be hi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.2.263
更新日期:1985-02-01 00:00:00
abstract::The in vitro activity of the azasordarin GW 471558 was compared with those of amphotericin B, flucytosine, itraconazole, and ketoconazole against 177 clinical isolates of Candida spp. GW 471558 showed potent activity against Candida albicans, Candida glabrata, and Candida tropicalis, even against isolates with decreas...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.6.1905-1907.2001
更新日期:2001-06-01 00:00:00
abstract::The EmbCAB proteins have been considered a target for ethambutol (EMB). Mutations in embCAB are known to confer most EMB resistance. However, the knowledge about the effects of embCAB mutations on the EMB resistance level and about the role of mutation-mutation interactions is limited in China. Here, we sequenced embC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01279-17
更新日期:2017-12-21 00:00:00
abstract::As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will be increasingly relied upon to treat infections and to lower the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01273-20
更新日期:2020-12-16 00:00:00