Abstract:
:Pseudomonas aeruginosa pneumonia remains a difficult therapeutic problem. Optimal doses and modes of administration of single agents often do not result in acceptable outcomes. Further, emergence of resistance occurs frequently in this setting with single-agent chemotherapy. The purpose of these experiments was to evaluate combination chemotherapy with meropenem plus tobramycin for P. aeruginosa in a murine pneumonia model. Neutropenia was induced by cyclophosphamide. Pharmacokinetics of meropenem and tobramycin were determined using a population pharmacokinetic approach. Both drugs were given at 4-h intervals. Meropenem was administered as total daily doses of 30 to 600 mg/kg of body weight, while tobramycin doses ranged from 50 to 400 mg/kg. Combination therapy evaluated all combinations of 50, 100, and 150 mg/kg/day of tobramycin doses with 60 or 300 mg/kg/day of meropenem. Total and drug-resistant organisms were enumerated. Meropenem alone had a near-maximal effect at 60 mg/kg/day (3.18 log10 [CFU/g] kill from stasis). The time > MIC in epithelial lining fluid (ELF) at this dose was 35.25% of 24 h. For tobramycin alone, the near-maximal effect was at 150 mg/kg/day and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) in ELF was 240.3. Resistance suppression occurred at an ELF AUC/MIC ratio of 110.6. For combination therapy, the near-maximal effect was reached at 60 mg/kg/day and 50 mg/kg/day of meropenem and tobramycin, which produced a 35.25% time > MIC in ELF and an ELF AUC/MIC ratio of 80.1. The interaction was additive. All combination regimens suppressed resistance. Combination therapy produced additive drug interaction and suppressed all resistance amplification. It is likely that optimal therapy for Pseudomonas aeruginosa pneumonia will involve a combination of agents.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Louie A,Liu W,Fikes S,Brown D,Drusano GLdoi
10.1128/AAC.02624-12subject
Has Abstractpub_date
2013-06-01 00:00:00pages
2788-92issue
6eissn
0066-4804issn
1098-6596pii
AAC.02624-12journal_volume
57pub_type
杂志文章abstract::Kingella kingae is the major pathogen causing osteoarticular infections (OAI) in young children in numerous countries. Plasmid-borne TEM-1 penicillinase production has been sporadically detected in a few countries but not in continental Europe, despite a high prevalence of K. kingae infections. We describe here for th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03562-14
更新日期:2014-10-01 00:00:00
abstract::Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01450-07
更新日期:2008-09-01 00:00:00
abstract::Candida albicans remains the leading causative agent of invasive fungal infection. Although the importance of filamentation in C. albicans pathogenesis has been extensively investigated, in vivo studies to date have been unable to dissect the role of this developmental process in the establishment of infection versus ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00628-06
更新日期:2006-10-01 00:00:00
abstract::Cefazolin was added to dialysis fluid in nine patients with renal failure undergoing peritoneal dialysis with 2 liters/h per exchange. With 50 mg/liter (three patients), the first measurable mean serum concentration was 3.7 mug/ml (range, 2.4 to 4.9 mug/ml) after three exchanges and was 30.3 mug/ml (range, 13.3 to 44....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.3.318
更新日期:1978-09-01 00:00:00
abstract::Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.8.2027
更新日期:1999-08-01 00:00:00
abstract::Susceptibility testing of laboratory strains and clinical isolates of Borrelia burgdorferi indicates that resistance to erythromycin is present in them. Evaluation of the MICs, minimal bactericidal concentrations, and kinetics of bacterial killing of erythromycin suggests that this resistance is increased by preexposu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3637-3640.2002
更新日期:2002-11-01 00:00:00
abstract::We demonstrate that xylitol can be added to polymethylmethacrylate (PMMA) bone cement to enhance the elution of daptomycin in terms of both the peak and sustained release of antibiotic. We also demonstrate that a PMMA-xylitol formulation optimized for daptomycin can be used to enhance the elution of both vancomycin an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00258-08
更新日期:2009-01-01 00:00:00
abstract::In the eubacterial cell, the peptidoglycan is perpetually hydrolyzed throughout the cell cycle by different enzymes such as lytic transglycosylases, endopeptidases, and amidases. In Escherichia coli, four N-acetylmuramoyl-l-alanine amidases, AmiA, -B, -C, and -D, are present in the periplasm. AmiA, -B, and -C are solu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01520-07
更新日期:2009-07-01 00:00:00
abstract::Norfloxacin is a quinolone (pyridonecarboxylic acid derivative) effective against Pseudomonas aeruginosa infections. We studied the effects of this drug on DNA metabolism in P. aeruginosa. Norfloxacin inhibits DNA replication immediately on its addition to a logarithmically growing culture of P. aeruginosa. It inhibit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.1.1
更新日期:1986-01-01 00:00:00
abstract::Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02394-19
更新日期:2020-04-21 00:00:00
abstract::The deduced amino acid sequence of Campylobacter jejuni Tet(O), cloned in Escherichia coli, has shown that it contains the five highly conserved sequences of the GTP-binding domain found in other GTPases. Asn-128 belongs to the G4 motif of such a domain and is involved in hydrogen bonding with the guanine ring of the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.12.2645
更新日期:1993-12-01 00:00:00
abstract::The stage-dependent susceptibility of Plasmodium falciparum to a short exposure to docetaxel (Taxotere) was evaluated by subjecting ring-infected, trophozoite-infected, and schizont-infected erythrocytes to a 5-h exposure to various concentrations of the drug. The schizont stage was shown to be the most sensitive stag...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.2.358
更新日期:1996-02-01 00:00:00
abstract::Racemic 2'-deoxy-3'-thiacytidine (BCH 189) is a dideoxycytidine analog having a sulfur atom in place of the 3' carbon. The enantiomers of BCH 189 have been resolved and found to be equipotent in antiviral activity against human immunodeficiency virus types 1 and 2. However, the (-)-enantiomer (3TC) is considerably les...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.1.202
更新日期:1992-01-01 00:00:00
abstract::An Escherichia coli strain with a plasmidic amikacin resistance has been selected for which the evidence strongly indicates that resistance is mediated by aminoglycoside phosphotransferase [APH(3')-II]: (i) this resistance was coupled with resistance against kanamycin and neomycin; (ii) partially purified APH(3')-II[A...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.344
更新日期:1981-09-01 00:00:00
abstract::Emtricitabine (FTC) is approved for the treatment of human immunodeficiency virus. FTC and clevudine (CLV) have activity against hepatitis B virus (HBV). This report summarizes the results of a double-blind, multicenter study of patients with chronic hepatitis B who had completed a phase 3 study of FTC and were random...
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
doi:10.1128/AAC.50.5.1642-1648.2006
更新日期:2006-05-01 00:00:00
abstract::Multiple injections of ofloxacin (subcutaneous or oral) in combination with a Lactobacillus casei preparation, LC9018 (subcutaneous), in mice infected intravenously with Mycobacterium fortuitum led to a marked delay in the incidence of spinning disease, a lowered incidence of gross renal lesions, and an increase in th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.4.632
更新日期:1990-04-01 00:00:00
abstract::The quinolones inhibit the A subunit of DNA gyrase in the presence of Mg2+ by interrupting the DNA breakage and resealing steps, and the latter step is also retarded without quinolones if Mg2+ is replaced by Ca2+. Pyrimido[1,6-a]benzimidazoles have been found to represent a new class of potent DNA gyrase inhibitors wh...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.163
更新日期:1995-01-01 00:00:00
abstract::Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and middle ear infections. The incidence of S. pneumoniae isolates that are not susceptible to penicillin has risen worldwide and may be above 20% in some countries. Beta-lactam antibiotic resistance in pneumococci is associated with sig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00429-15
更新日期:2015-01-01 00:00:00
abstract::Herpes simplex virus (HSV) types 1 and 2 (two strains each) were inactivated at different rates in vitro by 40 muM AgNO(3). The inactivation of HSV type 1 strains was virtually complete in 10 to 15 min, whereas almost half of the infectivity of HSV type 2 strains survived this exposure. One strain of type 1 inoculated...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.4.3.259
更新日期:1973-09-01 00:00:00
abstract::Enterobacteriaceae producing the OXA-48 carbapenemase are emerging worldwide, leaving few treatment options. Efficacy has been demonstrated in vivo with ceftazidime against a ceftazidime-susceptible OXA-48 isolate but not with imipenem despite maintaining susceptibility. The relationship between phenotype and in vivo ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01947-13
更新日期:2014-01-01 00:00:00
abstract::Alpha interferon and ribavirin are required in combination to achieve a sustained virological response in the treatment of hepatitis C virus (HCV) infection. Alpha interferon has direct antiviral activity and also enhances HCV-specific T-cell responses. Ribavirin has little direct activity against HCV but reduces hepa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3382-3389.2004
更新日期:2004-09-01 00:00:00
abstract::Here we completely sequenced four mcr-1-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00550-16
更新日期:2016-06-20 00:00:00
abstract::The activity of clavulanic acid alone and in combination with penicillin, amoxycillin, and carbenicillin was studied. Marked reductions in the minimum inhibitory concentrations (MICs) for a wide spectrum of beta-lactamase-producing clinical isolates were found. Of particular interest were the decreased MICs of penicil...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.3.389
更新日期:1978-03-01 00:00:00
abstract::Human immunodeficiency virus (HIV) Tat and gp120 intriguingly share the feature of being basic peptides that, once released by HIV(+) cells, bind to polyanionic heparan sulfate proteoglycans (HSPGs) on target uninfected cells, contributing to the onset of AIDS-associated pathologies. To identify multitarget anti-HIV p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01362-06
更新日期:2007-07-01 00:00:00
abstract::A multicenter susceptibility surveillance (the S.A.U.C.E. project) including 2,721 Streptococcus pneumoniae, 3,174 Streptococcus pyogenes, and 2,645 Haemophilus influenzae consecutive isolates was carried out in 25 hospitals all over Spain from November 2001 to October 2002 to evaluate the current epidemiology of resi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.5.1965-1972.2005
更新日期:2005-05-01 00:00:00
abstract::Unlike most antimicrobial peptides (AMPs), the main mode of action of the subclass of proline-rich antimicrobial peptides (PrAMPs) is not based on disruption of the bacterial membrane. Instead, PrAMPs exploit the inner membrane transporters SbmA and YjiL/MdtM to pass through the bacterial membrane and enter the cytoso...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00534-18
更新日期:2018-07-27 00:00:00
abstract::Replication of measles virus in BSC cells was studied in the presence of enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), a commonly used volatile anesthetic agent, and its isomer, isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether). At clinical concentrations of the anesthetics (up to 4%), ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.298
更新日期:1981-09-01 00:00:00
abstract::The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was sig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1219
更新日期:1996-05-01 00:00:00
abstract::After inducing mutagenesis with nitrosoguanidine, we used vancomycin enrichment in isolating auxotrophic mutants of Mycobacterium smegmatis. Compared with cycloserine and penicillin G, which are also cell wall inhibitors, vancomycin, with 24 h of exposure, produced less cell lysis and a greater reduction in viable cel...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.4.571
更新日期:1981-04-01 00:00:00
abstract::Since currently available therapies against HIV/AIDS still show important drawbacks, the development of novel anti-HIV treatments is a key issue. We recently characterized methylated oligoribonucleotides (mONs) that extensively inhibit HIV-1 replication in primary T cells at nanomolar concentrations. The mONs were sho...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05614-11
更新日期:2012-02-01 00:00:00