Abstract:
:Nacubactam is a novel non-β-lactam diazabicyclooctane β-lactamase inhibitor under development for the treatment of serious Gram-negative infections. This study assessed the efficacy of human-simulated epithelial lining fluid (ELF) exposure of nacubactam in combination with meropenem against AmpC-overproducing (n=4) and Klebsiella pneumoniae carbapenemase (KPC)-expressing (n=3) Pseudomonas aeruginosa isolates in the neutropenic murine lung infection model. Meropenem, nacubactam and meropenem-nacubactam (1:1 concentration ratio) minimum inhibitory concentrations (MICs) were determined in triplicate using broth microdilution. Regimens that provided ELF profiles mimicking those observed in humans given nacubactam 2 g q8h (1.5-h infusion) alone and in combination with a subtherapeutic ELF exposure of meropenem were administered 2 h after inoculation. Efficacy was assessed as the change in log10 colony-forming units (CFU)/lung at 24 h compared with 24-h meropenem monotherapy. Meropenem, nacubactam and meropenem-nacubactam MICs were 8->64, 128->256 and 2-16 mg/L, respectively. Meropenem and nacubactam monotherapy groups demonstrated bacterial growth over 24 h for each isolate. Against AmpC-overproducing and KPC-expressing P. aeruginosa isolates, meropenem-nacubactam resulted in -2.73±0.93 and -4.35±1.90 log10CFU/lung reduction, respectively, relative to meropenem monotherapy. Meropenem-nacubactam showed promising in-vivo activity against meropenem-resistant P. aeruginosa, indicative of a potential role for the treatment of infections caused by these challenging pathogens.
journal_name
Int J Antimicrob Agentsjournal_title
International journal of antimicrobial agentsauthors
Asempa TE,Motos A,Abdelraouf K,Bissantz C,Zampaloni C,Nicolau DPdoi
10.1016/j.ijantimicag.2019.10.019subject
Has Abstractpub_date
2020-02-01 00:00:00pages
105838issue
2eissn
0924-8579issn
1872-7913pii
S0924-8579(19)30299-7journal_volume
55pub_type
杂志文章abstract::Four hundred methicillin-resistant Staphylococcus aureus strains (MRSA) from different geographical areas in Malaysia were tested for mupirocin susceptibility using minimum inhibitory concentration (MIC) determination. The majority of these strains (98.75%) were susceptible to mupirocin with MICs of < or = 4 mg/l. Fif...
journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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abstract::The presence of the plasmid-mediated quinolone resistance determinants qnrA, qnrB, qnrS and aac(6')-Ib-cr was evaluated in a collection of 382 isolates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae collected between February and March 2006 for the nationwide Spanish GEIH-...
journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,评审
doi:10.1016/j.ijantimicag.2007.12.003
更新日期:2008-04-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/0924-8579(96)00014-3
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2017.01.023
更新日期:2017-06-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2006.08.007
更新日期:2006-11-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/s0924-8579(01)00363-6
更新日期:2001-08-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/s0924-8579(02)00364-3
更新日期:2003-02-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2018.10.003
更新日期:2019-02-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/s0924-8579(98)00107-1
更新日期:1999-07-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2014.07.021
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journal_title:International journal of antimicrobial agents
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更新日期:2018-12-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,meta分析,评审
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更新日期:2015-09-01 00:00:00
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journal_title:International journal of antimicrobial agents
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abstract::Cellulitis is a commonly seen clinical syndrome that is most often associated with beta-haemolytic streptococci and Staphylococcus aureus. Several medical conditions and a variety of procedures can predispose to the development of cellulitis by a common mechanism: venous and lymphatic compromise. The precise pathophys...
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更新日期:2000-03-01 00:00:00
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2009.03.021
更新日期:2009-11-01 00:00:00
abstract::Using a murine model of disseminated infection by Fusarium verticillioides, the efficacy of liposomal amphotericin (L-AmB) B at 10mg/kg body weight once daily and terbinafine (TRB) at 150 mg/kg body weight twice daily, alone and in combination, was evaluated. The combination of L-AmB with TRB was the only treatment ab...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:There are no effective therapies for patients with coronavirus disease-2019 (COVID-19). METHODS:Forty-one patients with confirmed COVID-19 were enrolled in the study and divided into two groups: artemisinin-piperaquine (AP) (n = 23) and control (n = 18). The primary outcome were the time taken to reach unde...
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pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
abstract::The aim of this study was to determine the rifampicin (RIF) resistance rate of meticillin-resistant Staphylococcus aureus (MRSA) amongst patients with MRSA bacteraemia who have or have not been exposed to RIF-containing antituberculous (anti-TB) treatment. From 2000 to 2008, patients with MRSA bacteraemia and previous...
journal_title:International journal of antimicrobial agents
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更新日期:2011-06-01 00:00:00