Abstract:
:Macrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to β-lactam antibiotics for treatment of severe community-acquired pneumonia. However, a beneficial effect of macrolides in treating Gram-negative bacterial airway infections, e.g., those caused by Pseudomonas aeruginosa, remains to be shown. Macrolide antibiotics have significant side effects, in particular, motility-stimulating activity in the gastrointestinal tract and promotion of bacterial resistance. In this study, EM703, a modified macrolide lacking antibiotic and motility-stimulating activities but with retained anti-inflammatory properties, was used as an adjunct treatment for experimental P. aeruginosa lung infection, in combination with a conventional antibiotic. Airway infections in BALB/cJRj mice were induced by nasal instillation of P. aeruginosa; this was followed by treatment with the quinolone levofloxacin in the absence or presence of EM703. Survival, inflammatory responses, and cellular influx to the airways were monitored. Both pretreatment and simultaneous administration of EM703 dramatically improved survival in levofloxacin-treated mice with P. aeruginosa airway infections. In addition, EM703 reduced the levels of proinflammatory cytokines, increased the numbers of leukocytes in bronchoalveolar lavage fluid, and reduced the numbers of neutrophils present in lung tissue. In summary, the findings of this study show that the immunomodulatory properties of the modified macrolide EM703 can be important when treating Gram-negative pneumonia, as exemplified by P. aeruginosa infection in this study.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Kasetty G,Bhongir RKV,Papareddy P,Herwald H,Egesten Adoi
10.1128/AAC.02761-16subject
Has Abstractpub_date
2017-08-24 00:00:00issue
9eissn
0066-4804issn
1098-6596pii
AAC.02761-16journal_volume
61pub_type
杂志文章abstract::MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s were 0.016 to 0.03 and 0.125 microgram/ml...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.7.1894-1899.2000
更新日期:2000-07-01 00:00:00
abstract::Mupirocin is a topical antimicrobial used to decolonize patients who carry methicillin-resistant Staphylococcus aureus (MRSA), and the topical agent retapamulin may be a potential alternative therapy. The goal of this study was to determine the in vitro activity of retapamulin as well as a panel of 15 antimicrobial ag...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01568-15
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00711-18
更新日期:2018-10-24 00:00:00
abstract::The Burkholderia cepacia complex (BCC) is a group of bacterial pathogens that are highly antibiotic resistant and associated with debilitating respiratory infections. Although bacteriophages of the BCC have been isolated and characterized, no studies have yet examined phage therapy against the BCC in vivo. In a caterp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01166-08
更新日期:2009-05-01 00:00:00
abstract::A47934, a peptide antibiotic produced by Streptomyces toyocaensis, belongs to the glycopeptide class of compounds which includes ristocetin and vancomycin. Incorporation studies with radioisotope-labeled substrates indicated that tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylate, acetate, and sulfate were ef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.10.1497
更新日期:1987-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.10.2392
更新日期:1996-10-01 00:00:00
abstract::Previously published literature reports various impacts of food on the oral bioavailability of piperaquine. The aim of this study was to use a population modeling approach to investigate the impact of concomitant intake of a small amount of food on piperaquine pharmacokinetics. This was an open, randomized comparison ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.02318-13
更新日期:2014-01-01 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::Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis in rabbits. Antifungal activity of the two polyenes in vitro was similar for the yeasts used in these experim...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.6.751
更新日期:1985-12-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03591-14
更新日期:2014-10-01 00:00:00
abstract::The gene coding for aminoglycoside 2'-N-acetyltransferase Ia [AAC(2')-Ia] from Providencia stuartii was amplified by PCR and cloned. The resulting construct, pACKF2, was transferred into Escherichia coli for overexpression of AAC(2')-Ia as a fusion protein with an N-terminal hexa-His tag. The fusion protein was isolat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.8.2238-2244.2001
更新日期:2001-08-01 00:00:00
abstract::Past genotypic studies of Mycobacterium tuberculosis may have incorrectly estimated the importance of specific drug resistance mutations due to a number of sampling biases including an overrepresentation of multidrug-resistant (MDR) isolates. An accurate assessment of resistance mutations is crucial for understanding ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.1.103-110.2000
更新日期:2000-01-01 00:00:00
abstract::This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (n...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02629-18
更新日期:2019-05-24 00:00:00
abstract::Imipenem-cilastatin concentrations in bile were measured in 12 cholecystectomy patients (group 1) and 12 patients with common duct drainage (group 2). Six patients in each group received 0.5 g, and six received 1.0 g intravenously over 30 to 60 min. In group 1, bile was collected a mean of 85 min postinfusion. The mea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.11.1718
更新日期:1987-11-01 00:00:00
abstract::Streptococcus agalactiae (group B Streptococcus [GBS]) is a Gram-positive bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy women. Although colonization is asymptomatic, GBS can be vertically transmitted to newborns peripartum, causing severe disease such as pneumonia and meningitis. Cu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01590-13
更新日期:2013-11-01 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::Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01723-15
更新日期:2015-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00784-09
更新日期:2009-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06374-11
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.6.1497
更新日期:1999-06-01 00:00:00
abstract::The recent widespread emergence of carbapenem resistance in Enterobacteriaceae is a major public health concern, as carbapenems are a therapy of last resort against this family of common bacterial pathogens. Resistance genes can mobilize via various mechanisms, including conjugation and transposition; however, the imp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00464-16
更新日期:2016-05-23 00:00:00
abstract::The pharmacokinetics of zidovudine (ZDV) are established in patients with various stages of human immunodeficiency virus (HIV) disease. This study was conducted to determine the pharmacokinetic parameters of ZDV in patients with asymptomatic HIV infection and liver disease. HIV-infected volunteers with normal renal fu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:1995-12-01 00:00:00
abstract::An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells we...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1116
更新日期:1996-05-01 00:00:00
abstract::Viral infections are among the main causes of death worldwide, and we lack antivirals for the majority of viruses. Heparin-like sulfated or sulfonated compounds have been known for decades for their ability to prevent infection by heparan sulfate proteoglycan (HSPG)-dependent viruses but only in a reversible way. We h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02001-20
更新日期:2020-11-17 00:00:00
abstract::The in vitro activity of LY 146032, a cyclic lipopeptide antibiotic belonging to the class of agents designated A21978C, was compared with those of vancomycin, cefpirome, cefotaxime, and clindamycin against selected gram-positive bacteria. The new drug inhibited all staphylococcal isolates, including methicillin-resis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.4.532
更新日期:1986-10-01 00:00:00
abstract::Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates are increasingly migrating from livestock into human and animal health care settings. Alternative substances are needed to overcome the drawbacks of currently available drugs used for MRSA eradication. The recombinant bacteriophage end...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00385-18
更新日期:2018-06-26 00:00:00
abstract::Zika virus (ZIKV), a flavivirus transmitted by mosquitoes, was an almost neglected pathogen until its introduction in the Americas in 2015 and its subsequent explosive spread throughout the continent, where it has infected millions of people. The virus has caused social and sanitary alarm, mainly due to its associatio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
doi:10.1128/AAC.00411-17
更新日期:2017-05-24 00:00:00
abstract::Artesunate (AS) is used in combination with amodiaquine (AQ) as first-line treatment for uncomplicated malaria in many countries. We investigated the effect of concomitant AS administration on the pharmacokinetics of AQ and compared concentrations of desethylamodiaquine (DEAQ), the main metabolite of AQ, in plasma bet...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.00673-07
更新日期:2008-12-01 00:00:00
abstract::Various steroids were tested for their effects upon gonococcal O2 consumption and glucose catabolism. The ability to inhibit gonococcal O2 uptake appeared to be related to the molecular configuration of the steroid. The presence of lipophilic groups enhanced inhibition, whereas the addition of hydrophilic groups marke...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.2.281
更新日期:1980-08-01 00:00:00