Abstract:
:Treating high-density bacterial infections is a challenging clinical problem. We have a paucity of new agents that can address this problem. Pseudomonas aeruginosa is a particularly difficult pathogen to treat effectively because of the plethora of resistance mechanisms it carries. Fosfomycin is an agent discovered circa 40 years ago. Recently, it has been resurrected in the United States and studied for intravenous therapy. We hypothesized that, to maximize its utility, it would require combination chemotherapy when used in a clinical circumstance in high-bacterial-burden infections. We chose to examine the combination of meropenem plus fosfomycin. These agents were studied in the hollow-fiber infection model. We utilized a fully factorial study design, looking at 2 doses of meropenem alone (1 and 2 g 8-hourly) and two doses of fosfomycin alone (6 and 8 g 8-hourly), as well as all possible combinations plus a no-treatment control. We used a high-dimensional model of 5 inhomogeneous differential equations with 5 system outputs to analyze all data simultaneously. Combination therapy outperformed all monotherapy regimens, with all combinations driving >6 log10 CFU/ml of bacterial killing. Combination therapy was able to counterselect resistance emergence (meropenem mutants being killed by the combination, as well as fosfomycin mutants being killed by the combination) in all regimens studied. The analysis demonstrated that the combination was significantly synergistic for bacterial cell killing and resistance suppression. Meropenem plus fosfomycin is a promising combination for therapy of high-burden Pseudomonas aeruginosa infections and requires further study.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Drusano GL,Neely MN,Yamada WM,Duncanson B,Brown D,Maynard M,Vicchiarelli M,Louie Adoi
10.1128/AAC.01682-18subject
Has Abstractpub_date
2018-11-26 00:00:00issue
12eissn
0066-4804issn
1098-6596pii
AAC.01682-18journal_volume
62pub_type
杂志文章abstract::Doxycycline is reported to impair second-generation parasite schizogony. The effects of doxycycline alone and combined with dihydroartemisinin were investigated in a murine malaria model. Doxycycline lowered the rate of parasite growth within 2 days, with maximum effect in 6 days. Addition of dihydroartemisinin led to...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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abstract::The efficacy of a loading dose of 20 mg of chloroquine per kg of body weight per os given at intervals during the first day was evaluated in 27 patients in Madagascar with Plasmodium falciparum malaria. The conventional regimen of 25 mg/kg over 3 days (schedule 1) was thus compared with a regimen of 30 mg/kg over 2 da...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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abstract::Kill-kinetic methods were used to provide data on the bactericidal activity of subinhibitory (0.5x MIC), inhibitory (1x MIC), and suprainhibitory (4x MIC) concentrations of LY146032 against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. These bactericidal activities were c...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.30.3.382
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00041-07
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abstract::Passive antibody administration is a potentially useful approach for the therapy of human Cryptococcus neoformans infections. To evaluate the efficacy of the human immunoglobulin G1 (IgG1) constant region against C. neoformans and to construct murine antibody derivatives with reduced immunogenicities and longer half-l...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00125-06
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.10.1502
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01597-09
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abstract::Two new fluorinated oxazolidinones, U-100592 and U-100766, were evaluated against more than 659 gram-positive and -negative organisms and compared with glycopeptides, erythromycin, clindamycin, clinafloxacin, and chloramphenicol. U-100592 and U-100766 were usually equally potent, but the MICs at which 90% of the isola...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.3.720
更新日期:1996-03-01 00:00:00
abstract::Treatment of Escherichia coli K-10 with 100 mug of chloramphenicol per ml for periods greater than 30 min leads to progressive lysis and killing of cells. The bactericidal action of the antibiotic is dependent on cell growth and physiology; only rapidly dividing cells are susceptible to killing; resting or slowly grow...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.6.748
更新日期:1975-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.4.429
更新日期:1975-10-01 00:00:00
abstract::The participation of trypanothione in clinical and experimental antimony (Sb) resistance in Leishmania panamensis was examined by using specific inhibitors. Buthionine sulfoximine (BSO) significantly reversed the resistance to trivalent Sb (Sb(III)) of promastigotes of experimentally derived Sb-resistant lines, suppor...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01075-08
更新日期:2008-12-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.6.1239
更新日期:1994-06-01 00:00:00
abstract::UK-18892 is a new aminoglycoside antibiotic, a derivative of kanamycin A structurally related to amikacin. It was found to be active against a wide range of pathogenic bacteria, including many gentamicin-resistant strains. The spectrum and degree of activity of UK-18892 were similar to those of amikacin, and differenc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.2.228
更新日期:1978-08-01 00:00:00
abstract::A rapid-flow cytofluorometric susceptibility test for in vitro amphotericin B testing of yeasts was evaluated and compared to the National Committee for Clinical Laboratory Standards (NCCLS) M27-T reference broth macrodilution method. The flow cytofluorometric method is based on the detection of decreased green fluore...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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