Abstract:
:While the neuraminidase (NA) inhibitor oseltamivir is currently our first line of defense against a pandemic threat, there is little information about whether in vitro testing can predict the in vivo effectiveness of antiviral treatment. Using a panel of five H5N1 influenza viruses (H5 clades 1 and 2), we determined that four viruses were susceptible to the drug in vitro (mean 50% inhibitory concentration [IC(50)], 0.1 to 4.9 nM), and A/Turkey/65-1242/06 virus was slightly less susceptible (mean IC(50), 10.8 nM). Two avian viruses showed significantly greater NA enzymatic activity (V(max)) than the human viruses, and the five viruses varied in their affinity for the NA substrate MUNANA (K(m), 64 to 300 muM) and for oseltamivir carboxylate (K(i), 0.1 to 7.9 nM). The protection of mice provided by a standard oseltamivir regimen (20 mg/kg/day for 5 days) also varied among the viruses used. We observed (i) complete protection against the less virulent A/chicken/Jogjakarta/BBVET/IX/04 virus; (ii) moderate protection (60 to 80% survival) against three viruses, two of which are neurotropic; and (iii) no protection against A/Turkey/65-1242/06 virus, which induced high pulmonary expression of proinflammatory mediators (interleukin-1alpha [IL-1alpha], IL-6, alpha interferon, and monocyte chemotactic protein 1) and contained a minor subpopulation of drug-resistant clones (I117V and E119A NA mutations). We found no correlation between in vitro susceptibility and in vivo protection (Spearman rank correlation coefficient rho = -0.1; P > 0.05). Therefore, the in vivo efficacy of oseltamivir against highly pathogenic H5N1 influenza viruses cannot be reliably predicted by susceptibility testing, and more prognostic ways to evaluate anti-influenza compounds must be developed. Multiple viral and host factors modulate the effectiveness of NA inhibitor regimens against such viruses and new, more consistently effective treatment options, including combination therapies, are needed.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Govorkova EA,Ilyushina NA,McClaren JL,Naipospos TS,Douangngeun B,Webster RGdoi
10.1128/AAC.01667-08subject
Has Abstractpub_date
2009-07-01 00:00:00pages
3088-96issue
7eissn
0066-4804issn
1098-6596pii
AAC.01667-08journal_volume
53pub_type
杂志文章abstract::Currently, CTX-M β-lactamases are among the most prevalent and most heterogeneous extended-spectrum β-lactamases (ESBLs). In general, CTX-M enzymes are susceptible to inhibition by β-lactamase inhibitors. However, it is unknown if the pathway to inhibition by β-lactamase inhibitors for CTX-M ESBLs is similar to TEM an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00089-11
更新日期:2011-07-01 00:00:00
abstract::The susceptibilities of 430 Campylobacter jejuni strains and 79 C. coli strains to six antimicrobial agents were tested and analyzed. The two sets of strains originated from retail market chicken and turkey samples and from humans, respectively, in Berlin, Germany. Two groups of isolates, one dating from 1991 and the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.12.3825-3830.2003
更新日期:2003-12-01 00:00:00
abstract::A unique group of viridans streptococci has been found in South Africa. These organisms were isolated in close temporal and physical proximity to the isolation of penicillin-resistant pneumococci. The strains were resistant to penicillin, oxacillin, the cephalosporins (all generations), piperacillin, azlocillin, and m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.5.702
更新日期:1983-11-01 00:00:00
abstract::We showed in a previous study that associations of antimicrobial peptides (AMPs), which are key components of the innate immune systems of all living species, with the fluoroquinolone enrofloxacin can successfully cure HeLa cell cultures of Mycoplasma fermentans and M. hyorhinis contamination. In the present work, the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01030-06
更新日期:2007-02-01 00:00:00
abstract::A reverse-phase high-pressure liquid chromatography method for the quantitation of sulbactam in plasma, urine, and tissue is described. The assay used the formation of an imidazole derivative followed by extraction with acetonitrile and dichloromethane and used UV absorbance for detection. The mobile phase consisted o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.2.231
更新日期:1986-08-01 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::The prevalence of three plasmid-mediated quinolone resistance determinants, QnrA, QnrB, and QnrS, among 526 nonreplicate clinical isolates of Enterobacter cloacae collected at a Taiwanese university hospital in 2004 was determined by PCR and colony hybridization, and the association of Qnr with the IMP-8 metallo-beta-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01195-06
更新日期:2007-04-01 00:00:00
abstract::In a single quantitative study, we measured acrA, acrB, tolC, mdfA, and norE expression in Escherichia coli clinical isolates by using real-time PCR. acrA and acrB overexpression strongly correlated with fluoroquinolone and multidrug resistance; tolC, mdfA, and norE expression did not. The order of abundance of efflux...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00996-10
更新日期:2011-02-01 00:00:00
abstract::Meglumine antimonate (Glucantime), a drug of choice for the treatment of leishmaniasis, is produced by the reaction of pentavalent antimony with N-methyl-D-glucamine, a carbohydrate derivative. We investigated the structure and composition of meglumine antimonate, which remain poorly understood, despite 50 years of us...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.5.1076
更新日期:1998-05-01 00:00:00
abstract::The in vitro and in vivo activities of a mixture of six oleane triterpene saponins, recovered from the methanolic extract of the leaves of the Vietnamese plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral Leishmania strains. The in vitro 50% inhibitory concentration (IC(50)) against intrace...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.1.130-136.2004
更新日期:2004-01-01 00:00:00
abstract::By means of a stepwise selection procedure, mutants capable of growing in the presence of relatively high multiplicities of a bacteriocin from Streptococcus mutans GS-5 were obtained from a sensitivie strain of Streptococcus pyogenes. Mutacin-neutralizing activity of cell extracts containing receptor protein was exami...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.2.151
更新日期:1980-02-01 00:00:00
abstract::At least four broad-spectrum efflux pumps (Mex) are involved in elevated intrinsic antibiotic resistance as well as in acquired multidrug resistance in Pseudomonas aeruginosa. Substrate specificity of the Mex pumps has been shown to be determined by the cytoplasmic membrane component (MexB, MexD, MexF, and MexY) of th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.7.2169-2173.2002
更新日期:2002-07-01 00:00:00
abstract::Cell-free amino acid incorporation using ribosomes from strains of either Clostridium perfringens or Bacteroides fragilis was shown to be susceptible to inhibition by streptomycin and gentamicin. Ribosomes bound dihydrostreptomycin as effectively as ribosomes from Escherichia coli. No inactivation of streptomycin or g...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.1.7
更新日期:1979-01-01 00:00:00
abstract::The effects of renal impairment on the pharmacokinetics of ceftriaxone in humans were examined after intravenous infusion of a 1-g dose over 15 min to 30 renally impaired patients. The study included 12 dialysis patients and 18 patients with severe, moderate, or mild renal impairment. Plasma and, where appropriate, ur...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.4.438
更新日期:1984-04-01 00:00:00
abstract::Heteroresistance refers to the presence, within a large population of antimicrobial-susceptible microorganisms, of subpopulations with lesser susceptibilities. Ceftaroline is a novel cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to detect the prevalen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02685-13
更新日期:2014-06-01 00:00:00
abstract::In a 1964 study of the pharmacokinetic determinants of penicillin cure of gonococcal urethritis, 45 male prisoner volunteers were experimentally infected with strains of Neisseria gonorrhoeae having known in vitro penicillin susceptibility. After developing urethritis, subjects received intramuscular penicillin G and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.4.587
更新日期:1979-04-01 00:00:00
abstract::We investigated the contribution of multidrug resistance-associated protein 2 (MRP2) to the secretory transport of grepafloxacin and compared its functional role with that of P-glycoprotein (P-gp) by using Sprague-Dawley rats (SDRs) and Eisai hyperbilirubinemic rats (EHBRs), in which MRP2 is hereditarily defective. In...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.2.344-349.2002
更新日期:2002-02-01 00:00:00
abstract::Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.8.1959
更新日期:1998-08-01 00:00:00
abstract::A comparison was made of the in vitro activity of ciprofloxacin (Bay o 9867) with nine other antibiotics against isolates of Campylobacter jejuni, Salmonella spp., Shigella spp., Yersinia enterocolitica, Clostridium difficile, Vibrio spp., and Escherichia coli. Minimum inhibitory concentrations of ciprofloxacin were t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.4.504
更新日期:1984-04-01 00:00:00
abstract::Fluconazole, an inhibitor of certain human cytochrome P-450 isozymes, is used for the prevention and treatment of a broad range of fungal infections that predominantly affect immunocompromised individuals. This study evaluated the influence of fluconazole on the steady-state pharmacokinetics of delavirdine, a nonnucle...
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.41.9.1892
更新日期:1997-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01682-18
更新日期:2018-11-26 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04441-14
更新日期:2015-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.10.3130-3137.2003
更新日期:2003-10-01 00:00:00
abstract::Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 microg/ml, respectively) and to low levels of teicoplanin (4 microg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.10.3892-3904.2004
更新日期:2004-10-01 00:00:00
abstract::The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01596-13
更新日期:2013-12-01 00:00:00
abstract::To determine whether low concentrations of aminoglycosides in combination with penicillin could effectively kill enterococci in vitro, we tested penicillin (20 micrograms/ml) in combination with decreasing concentrations of either streptomycin (20, 10, 5, and 1 micrograms/ml) or gentamicin (5, 3, 1, and 0.5 micrograms...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.6.944
更新日期:1980-12-01 00:00:00
abstract::The activities of cefotaxime, moxalactam, MK 0787 (N-formimidoyl thienamycin), ampicillin, oxacillin, vancomycin, and clindamycin were compared against gram-positive cocci. MK 0787 was the most active and moxalactam was the least active of these drugs, except against methicillin-resistant Staphylococcus aureus, where ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.4.553
更新日期:1981-10-01 00:00:00
abstract::Among hospitalized adults who received vancomycin for their skin and skin structure infection (SSSI), patients who experienced acute kidney injury (AKI) had considerably higher 30-day readmission rates. Nearly half of the observed 30-day readmissions were due to non-SSSI-related reasons, which is consistent with the p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01268-20
更新日期:2020-09-21 00:00:00
abstract::Nalidixic acid-resistant derivatives of Neisseria gonorrhoeae WR302 were identified and categorized into two classes on the basis of their susceptibilities to this antimicrobial agent. The MIC of nalidixic acid for the derivative strain MUG116 was fourfold greater than that for its isogenic parental strain WR302 (2 ve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.4.622
更新日期:1991-04-01 00:00:00
abstract::Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied. The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of inf...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.9.2424-2430.2000
更新日期:2000-09-01 00:00:00