In vitro and in vivo activities of AM-112, a novel oxapenem.
نویسندگان
چکیده
AM-112 [(1'R,5R,6R)-3-(4-amino-1,1-dimethyl-butyl)-6-(1'-hydroxyethyl)oxapenem-3-carboxylate] is a novel oxapenem compound which possesses potent beta-lactamase-inhibitory properties. Fifty-percent inhibitory concentrations (IC(50)s) of AM-112 for class A enzymes were between 0.16 and 2.24 micro M for three enzymes, compared to IC(50)s of 0.008 to 0.12 micro M for clavulanic acid. Against class C and class D enzymes, however, the activity of AM-112 was between 1,000- and 100,000-fold greater than that of clavulanic acid. AM-112 had affinity for the penicillin-binding proteins (PBPs) of Escherichia coli DC0, with PBP2 being inhibited by the lowest concentration of AM-112 tested, 0.1 micro g/ml. Ceftazidime was combined with AM-112 at 1:1 and 2:1 ratios in MIC determination studies against a panel of beta-lactamase-producing organisms. These studies demonstrated that AM-112 was effective at protecting ceftazidime against extended-spectrum beta-lactamase-producing strains and derepressed class C enzyme producers, reducing ceftazidime MICs by 16- and 2,048-fold. Similar results were obtained when AM-112 was combined with ceftriaxone, cefoperazone, or cefepime in a 1:2 ratio. Protection of ceftazidime with AM-112 was maintained against Enterobacter cloacae P99 and Klebsiella pneumoniae SHV-5 in a murine intraperitoneal sepsis model. The 50% effective dose of ceftazidime against E. cloacae P99 and K. pneumoniae SHV-5 was reduced from >100 and 160 mg/kg of body weight to 2 and 33.6 mg/kg, respectively, when it was combined with AM-112 at a 1:1 ratio. AM-112 demonstrates potential as a new beta-lactamase inhibitor.
منابع مشابه
In vitro activities of novel oxapenems, alone and in combination with ceftazidime, against gram-positive and gram-negative organisms.
Four novel oxapenem compounds (i.e., AM-112, AM-113, AM-114, and AM-115) were investigated for their beta-lactamase inhibitory activity against a panel of isolated class A, C, and D enzymes, which included expanded-spectrum beta-lactamase enzymes (ESBLs). The oxapenems were potent beta-lactamase inhibitors. Activity varied within the group, with AM-113 and AM-114 proving to be the most active c...
متن کاملIn vitro and in vivo evaluation of a novel testosterone transdermal delivery system (TTDS) using palm oil base
Objective (s): Transdermal preparations for testosterone are becoming popular because of their unique advantages such as avoidance of first-pass effect, convenience, improved bioavailability, and reduction of systemic side effects. A novel testosterone transdermal delivery system (TDDS) was developed using a palm oil base called HAMINTM (a commercial product) and tested using in vitro and in vi...
متن کاملEvaluation of γ-irradiation treatment on the antibacterial activities of Mentha piperita L. essential oils in vitro and in vivo systems (CLP inflammatory model)
Background: Mentha piperita L. essential oils have different antibacterial activity. In the present study, we investigated the effect of &gamma–irradiation on the antibacterial activities of Mentha piperita L. essential oils in vitro and in vivo systems. Materials and Methods: The aerial parts of peppermint were irradiated in a cobalt60 source with 0, 10 and 25 kGy absorbed doses. Then, t...
متن کاملComparative Analysis of Chemical Profile, Antioxidant, In-vitro and In-vivo Antidiabetic Activities of Juniperus foetidissima Willd. and Juniperus sabina L.
Fruit and leaves of junipers are commonly used internally as tea and pounded fruits are eaten to lower blood glucose levels in Anatolia. Thus, we aimed to evaluate antidiabetic and antioxidant potential and the chemical profile of Juniperus foetidissima Willd. and J. sabina L. in this study. In-vitro antidiabetic activities of leaf and fruit extracts were examined by their inhibitory activity o...
متن کاملComparative Analysis of Chemical Profile, Antioxidant, In-vitro and In-vivo Antidiabetic Activities of Juniperus foetidissima Willd. and Juniperus sabina L.
Fruit and leaves of junipers are commonly used internally as tea and pounded fruits are eaten to lower blood glucose levels in Anatolia. Thus, we aimed to evaluate antidiabetic and antioxidant potential and the chemical profile of Juniperus foetidissima Willd. and J. sabina L. in this study. In-vitro antidiabetic activities of leaf and fruit extracts were examined by their inhibitory activity o...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 47 5 شماره
صفحات -
تاریخ انتشار 2003