Abstract:
:To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three cephalosporins, cefotiam, cefmenoxime, and ceftriaxone, in a rabbit model of experimental Escherichia coli endocarditis after 4 days of treatment. The MBCs of cefotiam, cefmenoxime, and ceftriaxone for the E. coli strain were 0.5, 0.125, and 0.06 microgram/ml, respectively. Killing curves at 10 times the MBC were similar for the three cephalosporins. In serum, the elimination half-life of ceftriaxone was twice as much as the elimination half-life of cefotiam or cefmenoxime (2.8 +/- 0.45 versus 1.4 +/- 0.25 or 1.3 +/- 0.4 h, respectively). Ceftriaxone was much more effective than cefotiam. The bacterial titer in the vegetations (log10 CFU per gram of vegetation) was 7.56 +/- 1 with cefotiam and 2.41 +/- 2.6 with ceftriaxone, as their concentrations were 18 and 466 times higher, respectively, than their MBCs. Although ceftriaxone and cefmenoxime exhibited a similar rate of killing and percentage of protein binding, ceftriaxone was more effective than cefmenoxime at the same regimen of 15 mg/kg twice a day (3.08 +/- 1.1 versus 4.82 +/- 3.2 log10 CFU/g of vegetation). When antibiotic was given as a single daily injection of 30 mg/kg, the antibacterial effect persisted for ceftriaxone, but not for cefmenoxime. The longer elimination half-life and the higher local concentration/MBC ratio of ceftriaxone explained these results. The bacterial titer measured 24 h after the fourth injection of 30 mg of ceftriaxone per kg confirmed that this regimen prevented regrowth of bacteria. These results suggest that the local antibiotic level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed between the drugs in vivo. They also demonstrate that, provided that the dose is sufficient, a long-acting broad-spectrum cephalosporin may be effective in severe gram-negative infections, even when given at relatively long dosing intervals, in contrast with a rapidly cleared drug with the same intrinsic activity.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Pangon B,Joly V,Vallois JM,Abel L,Buré A,Brion N,Contrepois A,Carbon Cdoi
10.1128/aac.31.4.518subject
Has Abstractpub_date
1987-04-01 00:00:00pages
518-22issue
4eissn
0066-4804issn
1098-6596journal_volume
31pub_type
杂志文章abstract::The experimental model of infected fibrin clots in rabbits was used to study the penetration and in vivo activity of cefixime against Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The respective MICs of cefixime against these strains were 0.25, 2, and 8 micrograms/ml. The clots were infected with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.913
更新日期:1986-12-01 00:00:00
abstract::The candidacidal activity of nitric oxide (NO) as delivered by a class of compounds termed diazeniumdiolates has been investigated. Diazeniumdiolates are stable agents capable of releasing NO in a biologically usable form at a predicted rate, and three such compounds were examined for activity. One compound, (Z)-1-[N-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.9.2342
更新日期:1998-09-01 00:00:00
abstract::Biofilms are complex communities of microorganisms that attach to surfaces and are embedded in a self-produced extracellular matrix. Since these cells acquire increased tolerance against antimicrobial agents and host immune systems, biofilm-associated infectious diseases tend to become chronic. We show here that the m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04465-14
更新日期:2015-01-01 00:00:00
abstract::Acquiring iron (Fe) is critical to the metabolism and growth of Mycobacterium tuberculosis. Disruption of Fe metabolism is a potential approach for novel antituberculous therapy. Gallium (Ga) has many similarities to Fe. Biological systems are often unable to distinguish Ga(3+) from Fe(3+). Unlike Fe(3+), Ga(3+) canno...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01543-13
更新日期:2013-12-01 00:00:00
abstract::Porphyromonas gingivalis is a bacterial pathogen associated with chronic periodontitis that results in destruction of the tooth's supporting tissues. The major virulence determinants of P. gingivalis are its cell surface Arg- and Lys-specific cysteine proteinases, RgpA/B and Kgp. Lactoferrin (LF), an 80-kDa iron-bindi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05100-11
更新日期:2012-03-01 00:00:00
abstract::The need for an accurate and rapid method of testing ampicillin susceptibility of Haemophilus influenzae, especially strains isolated from patients with meningitis and septicemia, is indisputable. Various methods have been employed for this purpose. Each has advantages and disadvantages. This report describes a modifi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.2.318
更新日期:1978-02-01 00:00:00
abstract::The susceptibility of 53 clinical isolates of Bacteroides fragilis to cephamycins was examined. Judging from the MICs for 50% of the strains tested, moxalactam was the most active, however, judging from the MICs for 90% of the strains tested, cefbuperazone was more effective than moxalactam. A correlation was observed...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.6.773
更新日期:1985-12-01 00:00:00
abstract::Malaria remains a global health burden partly due to Plasmodium parasite resistance to first-line therapeutics. The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an essential protein for blood-stage Plasmodium parasites, but details about its function during malaria's elusive liver stage are unclear...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01799-17
更新日期:2018-03-27 00:00:00
abstract::Streptococcus agalactiae (group B Streptococcus [GBS]) is a Gram-positive bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy women. Although colonization is asymptomatic, GBS can be vertically transmitted to newborns peripartum, causing severe disease such as pneumonia and meningitis. Cu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01590-13
更新日期:2013-11-01 00:00:00
abstract::The in vitro activity of UK31214, a kanamycin B derivative, was studied against 250 recent isolates and compared with other aminoglycosides. Against the Enterobacteriaceae (with the exception of Proteus mirabilis and Providencia stuartii) UK31214 and amikacin had similar degrees of activity (mode minimum inhibitory co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.3.298
更新日期:1980-03-01 00:00:00
abstract::Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) inhibited herpes simplex virus type 1 (HSV-1) replication, although HSV-1 DNA was synthesized at normal levels in Vero cells. Viral capsids and extracellular virions were inhibited, and HSV-1 protein synthesis decreased by 50%, although no specific HSV-1 protein faile...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.5.941
更新日期:1986-05-01 00:00:00
abstract::Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01009-20
更新日期:2020-12-16 00:00:00
abstract::The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase (RT) is rapidly selected in tissue culture following serial passage of wild-type virus in the presence of increasing concentrations of lamivudine (3TC). M184V is also associated with several alterations of RT enzymatic function in vitr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.11.4189-4194.2004
更新日期:2004-11-01 00:00:00
abstract::Parallel in vitro tests, assessing the inhibition of schizont maturation, were conducted with 31 fresh isolates of Plasmodium falciparum from Thailand, using artemisinin, doxycycline, and combinations of both. The activities of artemisinin and doxycycline are obviously not correlated. Both compounds showed consistent ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.1.262-264.2002
更新日期:2002-01-01 00:00:00
abstract::Caspofungin (CAS) is approved for second-line management of proven or probable invasive aspergillosis at a dose of 50 mg once daily (QD). Preclinical and limited clinical data support the concept of the dose-dependent antifungal efficacy of CAS with preservation of its favorable safety profile. Little is known, howeve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01912-12
更新日期:2013-04-01 00:00:00
abstract::A total of 201 critically ill patients were studied during 267 courses of gentamicin or tobramycin treatment (139 gentamicin courses and 128 tobramycin courses). Of these 267 courses, pharmacokinetic and clinical data were obtained for 240 (120 gentamicin and 120 tobramycin). The data collected for pharmacokinetic ana...
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.19.5.859
更新日期:1981-05-01 00:00:00
abstract::Plaque formation and dye uptake assays were used to measure the MICs of PD 127,391 and PD 131,628 against Rickettsia species. The MICs of PD 127,391 were 0.25 microgram/ml for Rickettsia rickettsii and 0.125 to 0.25 microgram/ml for Rickettsia conorii. The MICs of PD 131,628 were 0.25 to 0.5 microgram/ml for R. ricket...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.11.2529
更新日期:1992-11-01 00:00:00
abstract::The in vitro activity of MDL 62,879, a new peptide antibiotic that inhibits protein synthesis through an interaction with elongation factor Tu, against a wide range of recent clinical isolates of common aerobic gram-positive and anaerobic organisms was determined. MDL 62,879 was highly active against staphylococci (MI...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.4.746
更新日期:1993-04-01 00:00:00
abstract::Invasive pulmonary aspergillosis (IPA) is a life-threatening disease of immunocompromised patients that requires aggressive therapy. Detection of the disease and monitoring of the therapeutic response during IPA are complex, and current molecular diagnostics are not suitably robust. Here, we explored proteomic profile...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02482-14
更新日期:2014-06-01 00:00:00
abstract::The prophylactic efficacy of 17C91, a carbamate prodrug of atovaquone (ATQ), was investigated in a severe combined immunodeficient mouse model of Pneumocystis carinii pneumonia (PCP). At an oral dosage equivalent to 100 mg of ATQ per kg of body weight per day, 17C91 protected 9 of 10 mice from PCP and had a prophylact...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.10.2217
更新日期:1995-10-01 00:00:00
abstract::Cefoxitin resistance, but not resistance to clindamycin, erythromycin, lincomycin, or tetracycline, was transferred by a conjugation-like process from Bacteroides thetaiotaomicron UN101, a clinical isolate haboring four kinds of plasmids, to other Bacteroides species. Of a sample of 20 cefoxitin-resistant transconjuga...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.4.701
更新日期:1982-10-01 00:00:00
abstract::The in vitro activities of four fluoroquinolone compounds were tested against 92 Escherichia coli strains of ovine and caprine origin under aerobic and anaerobic incubation conditions. The four fluoroquinolones proved to be highly effective against the E. coli isolates tested. When bacteria were cultured anaerobically...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.10.2469
更新日期:1994-10-01 00:00:00
abstract::Antibacterial agents disrupt the ecological balance of the normal human microflora. Tigecycline, a member of a new class of antibiotics (glycylcyclines), has been shown to have a potent broad-spectrum activity against most gram-positive and gram-negative aerobic and anaerobic bacteria. The aim of the study was to inve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00373-06
更新日期:2006-10-01 00:00:00
abstract::Minocycline and valproic acid are potential adjuvant therapies for the treatment of human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine whether minocycline alone or in combination with valproic acid affected atazanavir plasma concentrations. Twelve adult HIV-i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00194-08
更新日期:2008-09-01 00:00:00
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
pub_type: 杂志文章
doi:10.1128/aac.31.8.1210
更新日期:1987-08-01 00:00:00
abstract::Triazoles are first-line agents for treating aspergillosis. The prevalence of azole resistance in Aspergillus fumigatus is increasing, and cross-resistance is a growing concern. In this study, the susceptibilities of 40 A. fumigatus clinical isolates were tested by using the CLSI method with amphotericin B, itraconazo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01141-13
更新日期:2013-11-01 00:00:00
abstract::Oral Fusobacterium nucleatum populations from 20 young, healthy children were examined for beta-lactamase production. Ten children (50%) harbored, altogether, 25 beta-lactamase-positive F. nucleatum isolates that were identified as F. nucleatum subsp. polymorphum, F. nucleatum subsp. nucleatum, and F. nucleatum subsp....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.5.1270
更新日期:1999-05-01 00:00:00
abstract::The pharmacokinetics of the macrolide roxithromycin (RU 28965) were studied during and after administration of 150 mg every 12 h for 3 days (five doses) in six volunteers. The concentrations in serum, blister fluid, and urine were measured. Mean levels in serum taken at 1.5 h after the morning dose increased from 4.4 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.7.1051
更新日期:1987-07-01 00:00:00
abstract::It has recently become apparent that inflammatory reactions including nitric oxide (NO) release contribute to the outcome of pulmonary infections. To investigate the effect of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, on the pathogenesis of pneumococcal pneumonia, we inoculated CD(1) Swiss mice wit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.9.2283
更新日期:1999-09-01 00:00:00
abstract::The free ligand, deferroviridomycin A, and its iron(II) complex, viridomycin A, were detected in culture supernatant fluids of Streptomyces viridans 1671 and were structurally characterized as 4-hydroxy-3-nitrosobenzaldehyde and tris(4-hydroxy-3-nitrosobenzaldehydato-N3,O4)ferrate(II), respectively. We investigated th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.4.558
更新日期:1981-10-01 00:00:00