Abstract:
:There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs of 16 mg/liter and 64 mg/liter) and Klebsiella pneumoniae (MICs of 2 mg/liter and 64 mg/liter) using a dynamic hollow-fiber infection model over 7 days. Targeted peak concentrations of 300 mg/liter amikacin and/or 1,200 mg/liter fosfomycin as a 12-hourly dosing regimens were used. Quantitative cultures were performed to describe changes in concentrations of the total and resistant bacterial populations. The targeted starting inoculum was 108 CFU/ml for both strains. We observed that neither amikacin nor fosfomycin monotherapy was bactericidal against P. aeruginosa while both were associated with rapid amplification of resistant P. aeruginosa strains (about 108 to 109 CFU/ml within 24 to 48 h). For K. pneumoniae, amikacin but not fosfomycin was bactericidal. When both drugs were combined, a rapid killing was observed for P. aeruginosa and K. pneumoniae (6-log kill within 24 h). Furthermore, the combination of amikacin and fosfomycin effectively suppressed growth of resistant strains of P. aeruginosa and K. pneumoniae In conclusion, the combination of amikacin and fosfomycin was effective at maximizing bacterial killing and suppressing emergence of resistance against these clinical isolates.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Sime FB,Johnson A,Whalley S,Santoyo-Castelazo A,Montgomery AB,Walters KA,Lipman J,Hope WW,Roberts JAdoi
10.1128/AAC.01763-16subject
Has Abstractpub_date
2016-12-27 00:00:00issue
1eissn
0066-4804issn
1098-6596pii
AAC.01763-16journal_volume
61pub_type
杂志文章abstract::We report the ex vivo lysogenic transfer of erythromycin and tetracycline resistance genes among group A streptococci (GAS). Of 42 susceptible strains, 69% acquired erythromycin/tetracycline resistance when infected with purified supernatants from strain m46 culture containing the phage Φm46.1. A significant emm-type-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01318-09
更新日期:2010-10-01 00:00:00
abstract::The opportunistic Gram-negative pathogen Pseudomonas aeruginosa, known for its intrinsic and acquired antibiotic resistance, has a notorious ability to form biofilms, which often facilitate chronic infections. The evolutionary paths to antibiotic resistance have mainly been investigated in planktonic cultures and are ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00320-18
更新日期:2018-07-27 00:00:00
abstract::Pyrazinamide (PZA) has important sterilizing activity in tuberculosis (TB) chemotherapy. We describe trends, risk factors, and molecular epidemiology associated with PZA-resistant (PZA(r)) Mycobacterium tuberculosis in New York City (NYC). From 2001 to 2008, all incident culture-positive TB cases reported by the NYC D...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00764-15
更新日期:2015-10-01 00:00:00
abstract::Cryptococcus gattii isolates from the Pacific Northwest have exhibited higher fluconazole MICs than isolates from other sites. The mechanism of fluconazole resistance in C. gattii is unknown. We sought to determine the role of the efflux pumps Mdr1 and Pdr11 in fluconazole susceptibility. Using biolistic transformatio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01777-15
更新日期:2015-12-07 00:00:00
abstract::Dientamoeba fragilis is a commonly encountered trichomonad which has been implicated as a cause of gastrointestinal disease in humans. Despite the frequency of reports recording infections with this parasite, little research has been undertaken in terms of antimicrobial susceptibility. The aim of this study was to eva...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05125-11
更新日期:2012-01-01 00:00:00
abstract::The metallo-β-lactamase VIM-4, mainly found in Pseudomonas aeruginosa or Acinetobacter baumannii, was produced in Escherichia coli and characterized by biochemical and X-ray techniques. A detailed kinetic study performed in the presence of Zn²+ at concentrations ranging from 0.4 to 100 μM showed that VIM-4 exhibits a ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01486-09
更新日期:2011-03-01 00:00:00
abstract::A self-transferable plasmid of ca. 80 kb, pIP1204, conferred multiple-antibiotic resistance to Klebsiella pneumoniae BM4536, which was isolated from a urinary tract infection. Resistance to beta-lactams was due to the bla(TEM1) and bla(CTX-M) genes, resistance to trimethroprim was due to the dhfrXII gene, resistance t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.8.2565-2571.2003
更新日期:2003-08-01 00:00:00
abstract::Poly(DL-lactide-co-glycolide) (PLG) microparticles were developed as carriers for isoniazid and rifampin in order to improve compliance of tuberculous chemotherapy. Antitubercular drugs encapsulated in PLG polymers and injected in a single dose subcutaneously resulted in a sustained release (up to 6 weeks) of drugs in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.1.363-366.2001
更新日期:2001-01-01 00:00:00
abstract::Novel antibiotics approved by noninferiority trials may become less effective over time in two scenarios: (i) the treatment effect in studies of novel antibiotics may be consistently worse than studies of older antibiotics; (ii) when a decreasingly effective control arm is used in a series of noninferiority trials. Ou...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01597-20
更新日期:2020-10-20 00:00:00
abstract::Antibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed to the generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacterial virulence factors rather than their viability. Pseudomonas ae...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00732-11
更新日期:2012-01-01 00:00:00
abstract::A dexamethasone-treated rat model of cryptosporidiosis was used to evaluate the curative activity of paromomycin. Although eradication of the parasite could not be demonstrated, statistically significant decreases in oocyst excretion and in the intensity of ileal parasitism were observed in animals receiving 100 mg of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.7.1681
更新日期:1994-07-01 00:00:00
abstract::Fungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00640-15
更新日期:2015-10-01 00:00:00
abstract::The complete sequence of the carbapenem-resistance-conferring conjugative plasmid pLD209 from a Pseudomonas putida clinical strain is presented. pLD209 is formed by 3 well-defined regions: an adaptability module encompassing a Tn402-like class 1 integron of clinical origin containing blaVIM-2 and aacA4 gene cassettes,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02494-13
更新日期:2014-01-01 00:00:00
abstract::In this study, two identical copies of a 23S-5S gene cluster, which are separately situated within the Helicobacter pylori UA802 chromosome, were cloned and sequenced. Comparison of the DNA sequence of the H. pylori 23S rRNA gene with known sequences of other bacterial 23S rRNA genes indicated that the H. pylori UA802...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.12.2621
更新日期:1997-12-01 00:00:00
abstract::Invasive pulmonary aspergillosis is a life-threatening infection in lung transplant recipients; however, no studies of the pharmacokinetics and pharmacodynamics (PKPD) of echinocandins in transplanted lungs have been reported. We conducted a single-dose prospective study of the intrapulmonary and plasma PKPD of 150 mg...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.01647-09
更新日期:2010-08-01 00:00:00
abstract::The susceptibility of Saccharomyces cerevisiae JG436 multidrug transporter deletion mutant, Deltapdr5, to several antifungal agents was compared to that of JG436-derived JGCDR1 and JGCaMDR1 transformants, harboring the CDR1 and CaMDR1 genes, encoding the main drug-extruding membrane proteins of Candida albicans. The J...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.1.223-228.2001
更新日期:2001-01-01 00:00:00
abstract::Hypermutable Pseudomonas aeruginosa strains are found with high frequency in the lungs of patients with chronic infections and are associated with high antibiotic resistance rates. The in vivo consequences of hypermutation for treatment in a mouse model of lung infection using strain PAO1 and its hypermutable derivati...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.3.975-983.2006
更新日期:2006-03-01 00:00:00
abstract::Persister cells are highly tolerant to different antibiotics and are associated with relapsing infections. In order to understand this phenomenon further, we exposed a transposon library to a lethal concentration of ampicillin, and mutants that survived were identified by transposon sequencing (Tn-Seq). We determined ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01617-16
更新日期:2016-10-21 00:00:00
abstract::Seventy-one strains of 15 species of rapidly growing mycobacteria were studied for their susceptibilities to fatty acids with 2 to 20 carbons by the agar dilution method at pH 7.0. Most mycobacteria other than potential pathogens (Mycobacterium fortuitum and Mycobacterium chelonei) were resistant to saturated fatty ac...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.2.164
更新日期:1984-08-01 00:00:00
abstract::Diethylpyrocarbonate (DEPC) treatment of interferon (IF) inducers was studied both in vitro and in vivo. DEPC did not affect the antiviral activity of poly(I.C), statolon, or reovirus in cultured chicken embryo fibroblast cells, but the activities of poly(I.C), statolon, and MU9 replicative form in cultured mouse embr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.4.675
更新日期:1976-04-01 00:00:00
abstract::Anidulafungin concentrations were quantified with high-pressure liquid chromatography (HPLC) and UV detection of the ascites fluid and pleural effusion of 10 adult critically ill patients. Samples were collected from ascites fluid and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulaf...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02326-17
更新日期:2018-03-27 00:00:00
abstract::A DNA probe was developed by inserting, in the SmaI site of pBluescript sK, a 528-bp fragment of the gene responsible for intrinsic resistance to beta-lactam antibiotics in Staphylococcus aureus (mec determinant). The mec probe provided a useful tool for the rapid identification of the intrinsic resistance trait and f...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.3.575
更新日期:1991-03-01 00:00:00
abstract::Nonreplicating bacteria are known to be (or at least commonly thought to be) refractory to antibiotics to which they are genetically susceptible. Here, we explore the sensitivity to killing by bactericidal antibiotics of three classes of nonreplicating populations of planktonic bacteria: (i) stationary phase, when the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02360-18
更新日期:2019-06-24 00:00:00
abstract::Serial passage of Pseudomonas aeruginosa ATCC 27853 or Escherichia coli ATCC 25922 on agar with subinhibitory concentrations of norfloxacin rapidly produced isolates with minimal inhibitory concentrations (MICs) of norfloxacin up to 512-fold higher than that for the original strain. Although MICs of seven unrelated an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.1.188
更新日期:1983-01-01 00:00:00
abstract::Free-living amoebae of the genus Acanthamoeba are causing serious chronic conditions such as destructive keratitis in contact lens wearers or granulomatous amoebic encephalitis in individuals with compromised immune systems. Both are characterized by the lack of availability of sufficiently effective and uncomplicated...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.3.695-701.2002
更新日期:2002-03-01 00:00:00
abstract::The susceptibilities of Streptococcus pneumoniae (1,476 strains) and untypeable Haemophilus influenzae (1,676 strains) to various oral beta-lactam, macrolide-azalide, and fluoroquinolone antimicrobial agents were determined by broth microdilution. Organisms were isolated from specimens obtained from outpatients in six...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.43.8.1901
更新日期:1999-08-01 00:00:00
abstract::Levels of roxithromycin in serum and tissue were investigated in 29 subjects undergoing tonsillectomy. A total of 13 subjects received a single oral dose of 300 mg, and 16 received four oral doses 12 h apart as follows: a 300-mg loading dose followed by three 150-mg doses. Measurable levels of roxithromycin were prese...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.9.1461
更新日期:1988-09-01 00:00:00
abstract::Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly ac...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00204-17
更新日期:2017-09-22 00:00:00
abstract::The efficacy and safety of amoxicillin-clavulanic acid were compared with those of co-trimoxazole in the treatment of acute urinary tract infections. A total of 104 patients (mean age, 52 years) with clinical and laboratory evidence of acute urinary tract infection were enrolled in the study. Characteristics and infec...
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.28.5.693
更新日期:1985-11-01 00:00:00
abstract::A few international pneumococcal clones dominate the population of antibiotic-resistant pneumococci. Despite the scientific paradigm that a loss in fitness is the price for acquisition of resistance, these clones spread successfully. One hundred fifty-four isolates from adult patients with community-acquired pneumonia...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00250-11
更新日期:2011-10-01 00:00:00