Abstract:
:Ceftaroline fosamil is a cephalosporin with activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to characterize the dose-response relationship of ceftaroline fosamil against S. aureus in an immunocompromised murine pneumonia model, as well as to evaluate the efficacy of the humanized regimen of 600 mg intravenously (i.v.) every 12 h. Seventeen S. aureus (2 methicillin-susceptible Staphylococcus aureus [MSSA], 15 MRSA) isolates with ceftaroline MICs of 0.5 to 4 μg/ml were utilized. The pharmacokinetics of ceftaroline in serum and epithelial lining fluid (ELF) were evaluated to determine bronchopulmonary exposure profiles in infected and uninfected animals, using single and human-simulated doses. Serum fT>MIC (the percentage of time that free drug concentrations remain above the MIC) of 17% to 43% was required to produce a 1-log(10) kill in the dose-ranging studies. These targets were readily achieved with the humanized exposure profile, where decreases of 0.64 to 1.95 log(10) CFU were observed against 13 MRSA and both MSSA isolates tested. When taken as a composite, the fT>MICs required for stasis and a 1-log(10) kill were 16% and 41%, respectively. ELF concentrations were similar to serum concentrations across the dosing interval in infected and uninfected animals. The serum fT>MIC targets required in this lung infection model were similar to those observed with ceftaroline against S. aureus in a murine thigh infection model. Exposures simulating the human dose of 600 mg i.v. every 12 h achieved pharmacodynamic targets against MRSA and MSSA considered susceptible by current U.S. FDA breakpoints.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Bhalodi AA,Crandon JL,Biek D,Nicolau DPdoi
10.1128/AAC.01078-12subject
Has Abstractpub_date
2012-12-01 00:00:00pages
6160-5issue
12eissn
0066-4804issn
1098-6596pii
AAC.01078-12journal_volume
56pub_type
杂志文章abstract::Two types of transmissible plasmids which encode resistance to trimethoprim-sulfamethoxazole were found among five animal isolates of Salmonella krefeld. This is the first report of plasmid-mediated resistance to trimethoprim-sulfamethoxazole in Salmonella strains isolated in the United States. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.3.495
更新日期:1983-03-01 00:00:00
abstract::Iatrogenic Cushing's syndrome is an undesirable outcome of glucocorticoids treatment. It can be increased by pharmacologic interactions. Glucocorticoid therapy, given in association with ritonavir, and some azole treatments are causes of iatrogenic Cushing's syndrome. We present a patient with common-variable immunode...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00416-13
更新日期:2013-11-01 00:00:00
abstract::Human immunodeficiency virus (HIV) type 1 (HIV-1) variants were selected for resistance to the (+) and (-) enantiomers of a novel nucleoside analogue, 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine (dOTFC), by use of the infectious molecular clone HIV HXB2D and the human T-cell line MT-4. The dOTFC-resistant variants that w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.5.1127-1131.2000
更新日期:2000-05-01 00:00:00
abstract::An oligonucleoside methylphosphonate (ONMP) complementary to the splice acceptor site of immediate-early (IE) pre-mRNAs 4 and 5 (IE4,5SA) inhibits herpes simplex virus type 1 (HSV-1) growth in vitro and in infected animals. The antiviral effect appears to be due to inhibition of IE pre-mRNA 4 and 5 splicing and/or IE4...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.4.675
更新日期:1994-04-01 00:00:00
abstract::TP-434 is a novel, broad-spectrum fluorocycline antibiotic with activity against bacteria expressing major antibiotic resistance mechanisms, including tetracycline-specific efflux and ribosomal protection. The mechanism of action of TP-434 was assessed using both cell-based and in vitro assays. In Escherichia coli cel...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06187-11
更新日期:2012-05-01 00:00:00
abstract::Mycobactin biosynthesis in Mycobacterium tuberculosis facilitates iron acquisition, which is required for growth and virulence. The mycobactin biosynthesis inhibitor salicyl-AMS [5'-O-(N-salicylsulfamoyl)adenosine] inhibits M. tuberculosis growth in vitro under iron-limited conditions. Here, we conducted a single-dose...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00918-13
更新日期:2013-10-01 00:00:00
abstract::Resistance to rifampin in Mycobacterium tuberculosis results from mutations in the gene coding for the beta subunit of RNA polymerase (rpoB). At least 95% of rifampin-resistant isolates have mutations in rpoB, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.12.3298-3301.2000
更新日期:2000-12-01 00:00:00
abstract::A potential strategy that can be used to combat the worldwide AIDS epidemic is the development of a vaginal microbicide that prevents the sexual transmission of human immunodeficiency virus type 1 (HIV-1). Certain CC chemokines, including RANTES, MIP-1alpha, and MIP-1beta, might facilitate the development of such micr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.4.1497-1509.2006
更新日期:2006-04-01 00:00:00
abstract::Debio-025 is a synthetic cyclosporine with no immunosuppressive capacity but a high inhibitory potency against cyclophilin A (CypA)-associated cis-trans prolyl isomerase (PPIase) activity. A lack of immunosuppressive effects compared to that of cyclosporine was demonstrated both in vitro and in vivo. For three cyclosp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01324-07
更新日期:2008-04-01 00:00:00
abstract::Current data indicate that once-daily aminoglycoside therapy is as efficacious as traditional multiple daily dosing and equally or less toxic. Our experience with once-daily gentamicin, 6 mg/kg of body weight led to a 10% (3 of 33 patients) occurrence of documented ototoxicity after prolonged aminoglycoside exposure. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.2209
更新日期:1996-09-01 00:00:00
abstract::High-dose clindamycin (CLDM) and benzylpenicillin (PCG) are the recommended chemotherapeutic remedies for toxic shock-like syndrome caused by group A streptococci. One reason for this is that it has been shown that CLDM suppresses the expression of some exoproteins, e.g., SpeB, SpeA, and streptolysin O (Slo). We analy...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.1.88-96.2005
更新日期:2005-01-01 00:00:00
abstract::Stenotrophomonas maltophilia is an emerging nosocomial pathogen that displays high-level intrinsic resistance to a variety of structurally unrelated antimicrobial agents. Efflux mechanisms are known to contribute to acquired multidrug resistance in this organism, and indeed, one such multidrug efflux system, SmeDEF, w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3497-3503.2001
更新日期:2001-12-01 00:00:00
abstract::Antifungal effects of iron chelators (lactoferrin, deferoxamine, deferiprone, and ciclopirox) were tested alone and in combination with antifungal drugs against Aspergillus fumigatus B5233 conidia. Lactoferrin, ciclopirox, and deferiprone inhibited whereas deferoxamine enhanced fungal growth. Antifungal synergy agains...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01547-08
更新日期:2009-06-01 00:00:00
abstract::Azithromycin (AZI) is an azalide antibiotic with antimalarial activity that is considered safe in pregnancy. To assess its pharmacokinetic properties when administered as intermittent preventive treatment in pregnancy (IPTp), two 2-g doses were given 24 h apart to 31 pregnant and 29 age-matched nonpregnant Papua New G...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00771-09
更新日期:2010-01-01 00:00:00
abstract::The abilities of the H+-ATPase inhibitor N, N'-dicyclohexylcarbodiimide and the antibiotic ionophore nigericin to enhance the bactericidal effect of subinhibitory concentrations of gentamicin in two strains of Staphylococcus aureus were studied. Each compound significantly increased both gentamicin uptake and killing....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.3.440
更新日期:1983-09-01 00:00:00
abstract::Eight healthy male volunteers received 1 g of either ceftazidime or cefamandole as an intravenous infection. Serial blood samples were taken over the next 8 h. Urine samples were collected over 24 h. Levels of these antibiotics were measured in the fluid of blisters resulting from application of cantharides. The conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.356
更新日期:1981-09-01 00:00:00
abstract::Although it is generally believed that bactericidal and bacteriostatic drugs should not be combined in vivo, in vitro experiments using the checkerboard dilution technique revealed no antagonism between penicillin/cephalothin and rolitetracycline but rather additive or synergistic activity of either drug combination i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.5.802
更新日期:1976-11-01 00:00:00
abstract::The 747-bp cfiA gene, which encodes a metallo-beta-lactamase, and the regions flanking cfiA in six imipenem-resistant and four imipenem-susceptible Bacteroides fragilis strains isolated in Japan were analyzed by PCR and DNA sequencing. The nucleotide sequences of the cfiA genes (designated cfiA(1) to cfiA(10)) of all ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.3.979-985.2003
更新日期:2003-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:2005-05-01 00:00:00
abstract::In order to study the mechanism of insusceptibility of Spiroplasma citri to rifampin, we have cloned and sequenced its rpoB gene, which encodes the beta subunit of RNA polymerase. By comparison of the deduced amino acid sequence with sequences of beta subunits from susceptible and resistant bacteria, it was possible t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.858
更新日期:1996-04-01 00:00:00
abstract::Invasive pulmonary aspergillosis (IPA) is a devastating disease of immunocompromised patients. Pharmacodynamic (PD) examination of antifungal drug therapy in IPA is one strategy that may improve outcomes. The current study explored the PD target of posaconazole in an immunocompromised murine model of IPA against 10 A....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01279-12
更新日期:2013-01-01 00:00:00
abstract::The Infectious Diseases Society of America advocates trimethoprim-sulfamethoxazole (SXT) as initial therapy for females with acute uncomplicated bacterial cystitis in settings where the prevalence of SXT resistance does not exceed 10 to 20%. To determine trends in the activities of SXT, ampicillin, ciprofloxacin, and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.8.2540-2545.2002
更新日期:2002-08-01 00:00:00
abstract::The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.5.815
更新日期:1987-05-01 00:00:00
abstract::The in vitro susceptibility of Brucella melitensis was examined vis-a-vis the clinical outcome in 75 patients with brucellosis. The initial MICs for Brucella isolates from patients who relapsed and from those who did not were similar. Furthermore, the MICs for isolates from patients whose infections relapsed were no d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.958
更新日期:1986-12-01 00:00:00
abstract::The simian immunodeficiency virus (SIV)-newborn rhesus macaque model of AIDS can be used to study directly the virulence of viral mutants which are resistant to antiviral drugs. A viral mutant called SIVmac79A6.1, isolated from an SIV-infected macaque after prolonged zidovudine treatment, was found to have a double-ba...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.2.278
更新日期:1997-02-01 00:00:00
abstract::Visceral leishmaniasis is a neglected tropical disease that causes significant morbidity and mortality worldwide. Characterization of the pharmacokinetics and pharmacodynamics of antileishmanial drugs in preclinical models is important for drug development and use. Here we investigated the pharmacodynamics and drug di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00497-17
更新日期:2017-08-24 00:00:00
abstract::The susceptibility of 26 strains of varicella-zoster virus to cytarabine was tested in vitro by measuring reduction in number and size of plaques using human foreskin fibroblast cells. Most strains showed 50% reduction of plaque number by 0.125 mug of cytarabine per ml or less. Cytarabine levels in sera of 12 patients...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.3.229
更新日期:1975-03-01 00:00:00
abstract::The effects of probenecid on the pharmacokinetics and renal clearance of acyclovir were studied in humans. Acyclovir (5 mg/kg) was given as a 1-h infusion to three volunteers with normal renal function both before and after oral administration of probenecid (1 g). The kinetics were well described by a two-compartment ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.5.804
更新日期:1982-05-01 00:00:00
abstract::Seven hundred twenty-three isolates of Moraxella catarrhalis obtained from outpatients with a variety of infections in 30 medical centers in the United States between 1 November 1994 and 30 April 1995 were characterized in a central laboratory. The overall rate of beta-lactamase production was 95.3%. When the National...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.40.12.2884
更新日期:1996-12-01 00:00:00
abstract::The biological availability of cefoxitin administered rectally in the form of suppositories was examined in six human subjects by a cross-over design. Four different suppository systems containing adjuvants expected to enhance the absorption of the drug were studied. The presence of sodium salicylate and a nonionic su...
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.28.2.211
更新日期:1985-08-01 00:00:00