Abstract:
:The role of inhalational combination therapy when treating carbapenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae with newer beta-lactam/beta-lactamase inhibitors has not been established. Using a 72-h in vitro pharmacodynamic chemostat model, we simulated the human exposures achieved in epithelial lining fluid (ELF) following intravenous treatment with ceftazidime-avibactam (CZA) 2.5 g every 8 h (q8h) alone and in combination with inhaled amikacin (AMK-I) 400 mg q12h, a reformulated aminoglycoside designed for inhalational administration, against three P. aeruginosa isolates (CZA [ceftazidime/avibactam] MICs, 4/4 to 8/4 μg/ml; AMK-I MICs, 8 to 64 μg/ml) and three K. pneumoniae isolates (CZA MICs, 1/4 to 8/4 μg/ml; AMK-I MICs, 32 to 64 μg/ml). Combination therapy resulted in a significant reduction in 72-h CFU compared with that of CZA monotherapy against two of three P. aeruginosa isolates (-4.14 log10 CFU/ml, P = 0.027; -1.42 log10 CFU/ml, P = 0.020; and -0.4 log10 CFU/ml, P = 0.298) and two of three K. pneumoniae isolates (0.04 log10 CFU/ml, P = 0.963; -4.34 log10 CFU/ml, P < 0.001; and -2.34 log10 CFU/ml, P = 0.021). When measured by the area under the bacterial growth curve (AUBC) over 72 h, significant reductions were observed in favor of the combination regimen against all six isolates tested. AMK-I combination therapy successfully suppressed CZA resistance development in one K. pneumoniae isolate harboring blaKPC-3 that was observed during CZA monotherapy. These studies suggest a beneficial role for combination therapy with intravenous CZA and inhaled AMK when treating pneumonia caused by carbapenem-resistant Gram-negative bacteria.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Almarzoky Abuhussain SS,Kuti JL,Nicolau DPdoi
10.1128/AAC.00113-18subject
Has Abstractpub_date
2018-06-26 00:00:00issue
7eissn
0066-4804issn
1098-6596pii
AAC.00113-18journal_volume
62pub_type
杂志文章abstract::The pharmacodynamic properties of levofloxacin (an optically active isomer of ofloxacin), ofloxacin, and ciprofloxacin, alone and in combination with rifampin, were evaluated over 24 to 48 h against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA 1199 and MRSA 494, respectively)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.12.2702
更新日期:1994-12-01 00:00:00
abstract::The aim of this study was to reveal population pharmacokinetics and assess the efficacies of various dosage regimens of sulbactam in terms of the probability of target attainment with this agent over a range of MICs. Monte Carlo simulations were performed to determine the probability of attaining specific pharmacodyna...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00342-13
更新日期:2013-07-01 00:00:00
abstract::Oral doses of norfloxacin (80 mg/kg of body weight per day) and ciprofloxacin (25 and 80 mg/kg/day) and intramuscular doses of teicoplanin (5 mg/kg/day), all administered once a day for 10 days, were evaluated as a means of preventing encrusted cystitis caused by Corynebacterium group D2. Zinc disks dipped into a 24-h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.12.2587
更新日期:1991-12-01 00:00:00
abstract::Subinhibitory concentrations of antibiotics have been shown to enhance biofilm formation in multiple bacterial species. While antibiotic exposure has been associated with modulated expression of many biofilm-related genes, the mechanisms of drug-induced biofilm formation remain a focus of ongoing research efforts and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01603-17
更新日期:2017-12-21 00:00:00
abstract::Although antimicrobial agents are effective therapy for early Lyme disease, optimal treatment schedules have not been conclusively established. The efficacy of various dosages of eight antibiotics used for borreliosis treatment was evaluated for C3H/HeNCrIBR mice, which reproducibly develop persistent infection, arthr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.7.1567
更新日期:1994-07-01 00:00:00
abstract::The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster. Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin re...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.4.1291-1296.2003
更新日期:2003-04-01 00:00:00
abstract::The activity of azlocillin and mezlocillin, new semisynthetic ureido penicillins, was investigated and compared with that of other known beta-lactam antibiotics. At a concentration of 25 mug/ml, azlocillin inhibited 74% of Enterobacter, 97% of Proteus mirabilis, 64% of Citrobacter, 91% of Pseudomonas aeruginosa, and 8...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.6.930
更新日期:1978-06-01 00:00:00
abstract::Population distributions and quality control data for strains of Pseudomonas aeruginosa tested for gentamicin susceptibility on six lots of Mueller-Hinton agar were analyzed. The lots of agar were used in three University of Washington hospitals from April 1975 through October 1977. The analyses indicated that the per...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.3.360
更新日期:1978-09-01 00:00:00
abstract::Bisbenzamidines, such as pentamidine isethionate, are aromatic dicationic compounds that are active against Pneumocystis and other microbes but are oftentimes toxic to the host. To identify potential anti-Pneumocystis agents, we synthesized bisbenzamidine derivatives in which the parent compound pentamidine was modifi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00126-06
更新日期:2006-07-01 00:00:00
abstract::We have quantified the biological cost of VanA-type glycopeptide resistance due to the acquisition of the resistance operon by methicillin-resistant Staphylococcus aureus (MRSA) from Enterococcus sp. Exponential growths of recipient strain HIP11713, its transconjugant VRSA-1, VRSA-5, and VRSA-6 were compared in the ab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01702-08
更新日期:2009-06-01 00:00:00
abstract::Staphylococcus epidermidis is one of the most frequent causes of device-associated infections, because it is known to cause biofilms that grow on catheters or other surgical implants. The persistent increasing resistance of S. epidermidis and other coagulase-negative staphylococci (CoNS) has driven the need for newer ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00504-13
更新日期:2013-10-01 00:00:00
abstract::Two nitrosoureas, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), with strong carbamoylating and weak alkylating activities, interfered with the induction of potassium leakage and lethal action of amphotericin B (AmB) on Candida albicans. 2-Cyclohexyl isocyanate, t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.3.327
更新日期:1988-03-01 00:00:00
abstract::Structural analysis of two new beta-lactam antibiotics, A16884A and A16886B, indicated that they, like cephalosporin C, were composed of modified valine and cysteine residues, and alpha-aminoadipic acid. However, acid hydrolysis of A16886B and A16884A produced three times as much glycine as did hydrolysis of cephalosp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.1.3.242
更新日期:1972-03-01 00:00:00
abstract::A preliminary study was conducted with netilmicin, a new aminoglycoside antibiotic. Its effectiveness was evaluated in vitro against 546 strains of Enterobacteriaceae and Pseudomonas aeruginosa isolated from clinical material. Its effectiveness against gentamicin-susceptible strains was roughly similar to that of gent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.12.4.503
更新日期:1977-10-01 00:00:00
abstract::OXA-48-like carbapenemases have only recently emerged in Europe. OXA-162 is a rare OXA-48 variant usually coexpressed with extended-spectrum β-lactamases. Here, we report the identification of the first OXA-162 carbapenemase-producing Klebsiella pneumoniae isolates, which coexpressed an AmpC cephalosporinase (DHA-1), ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01514-15
更新日期:2015-12-14 00:00:00
abstract::Ninety-two strains of Yersinia pestis recovered over a 21-year period were evaluated for susceptibility to traditional and newer antimicrobial agents. In vitro resistance was noted only against rifampin and imipenem (approximately 20% of strains). The most active compounds (MIC at which 90% of the isolates tested are ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.7.1995-1996.2000
更新日期:2000-07-01 00:00:00
abstract::The need for novel antibacterial strategies and the awareness of the importance of quorum sensing (QS) in bacterial infections have stimulated research aimed at identifying QS inhibitors (QSIs). However, clinical application of QSIs identified so far is still distant, likely due to their unsuitability for use in human...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01952-12
更新日期:2013-02-01 00:00:00
abstract::A remarkably high rate of adverse events is associated with the use of trimethoprim-sulfamethoxazole in patients with human immunodeficiency virus type 1 infection. We examined the efficacies of sulfonamides alone in the prevention of Pneumocystis carinii pneumonitis, with the assumption that at least some of the adve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.962
更新日期:1996-04-01 00:00:00
abstract::The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and 0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.5.1253
更新日期:1998-05-01 00:00:00
abstract::ST-246, a novel compound that inhibits egress of orthopoxvirus from infected cells, is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, placebo-controlled, escalating multiple-dose study was conducted to determine the safety, tolerability, and ph...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01689-09
更新日期:2010-06-01 00:00:00
abstract::Enterobacteriaceae producing the Ambler class D OXA-48 carbapenemase, combined with additional resistance mechanisms, such as permeability defects or cocarriage of class A, B, or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 Enterobacteriaceae ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00592-18
更新日期:2018-11-26 00:00:00
abstract::The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis. Mice were treated with ceftriaxone or saline solution for 1 month, commencing during the early (3 weeks) or chronic (4 months) stages of infection with Borrelia burgdorferi. Tissues from mice were tested for infection by cultu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01050-07
更新日期:2008-05-01 00:00:00
abstract::Human immunodeficiency virus (HIV) is the primary etiologic agent responsible for the AIDS pandemic. In this work, we used a chimeric recombinant protein strategy to test the possibility of irreversibly destroying the HIV-1 virion using an agent that simultaneously binds the Env protein and viral membrane. We construc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00309-13
更新日期:2013-10-01 00:00:00
abstract::We have used the endogenous reverse transcriptase reaction of viral core particles from duck liver to elucidate the mechanism of inhibition of duck hepatitis B virus (DHBV) replication by the nucleoside analog (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC). As is the case in human immunodeficiency virus replication, 3...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.7.1430
更新日期:1995-07-01 00:00:00
abstract::Foscarnet is widely used for the treatment of acyclovir-resistant herpesvirus infections, and foscarnet-resistant herpesvirus infections are a serious concern in immunocompromised patients. Twenty-seven single-plaque isolates of herpes simplex virus type 1 (HSV-1) resistant to foscarnet were selected from foscarnet- a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.2.606-611.2005
更新日期:2005-02-01 00:00:00
abstract::The efficacy of ticarcillin-clavulanic acid was compared with the efficacies of standard antistaphylococcal agents (flucloxacillin, oxacillin, nafcillin, and vancomycin) and ticarcillin in an experimental model of Staphylococcus aureus endocarditis. Therapy was either initiated soon (8 h) after infection, when numbers...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.2.458
更新日期:1992-02-01 00:00:00
abstract::A new natural TEM derivative, named TEM-87, was identified in a Proteus mirabilis isolate from an Italian hospital. Compared to TEM-1, TEM-87 contains the following mutations: E104K, R164C, and M182T. Kinetic analysis of TEM-87 revealed extended-spectrum activity against oxyimino cephalosporins (preferentially ceftazi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.3.925-928.2002
更新日期:2002-03-01 00:00:00
abstract::We report the identification of a carbapenem-resistant, hypervirulent Klebsiella pneumoniae (hvKp) strain which produced the carbapenemase VIM-1. Genomic analysis showed that the strain belonged to sequence type ST23 and serotype K1, a major hvKp clone, and harbored three resistance-encoding plasmids. Among them, a bl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01056-19
更新日期:2019-08-23 00:00:00
abstract::The in vitro activity of UK31214, a kanamycin B derivative, was studied against 250 recent isolates and compared with other aminoglycosides. Against the Enterobacteriaceae (with the exception of Proteus mirabilis and Providencia stuartii) UK31214 and amikacin had similar degrees of activity (mode minimum inhibitory co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.3.298
更新日期:1980-03-01 00:00:00
abstract::The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentratio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.3.347
更新日期:1984-09-01 00:00:00