関: cefodizime sodium

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Cefodizime is a 3rd generation cephalosporin antibiotic with broad spectrum activity against aerobic gram positive and gram negative bacteria. Clinically, it has been shown to be effective against upper and lower respiratory tract infections, urinary tract infections, and gonorrhea. Cefodizime is a bactericidal antibiotic that targets penicillin-binding proteins (PBPs) 1A/B, 2, and 3 resulting in the eventual death of the bacterial cell. In vivo experimental models of infection showed that bacterial clearance by this drug is at least as effective compared with other 3rd generation cephalosporins. It has similar adverse effect profile to other 3rd generation cephalosporins as well, mainly being limited to gastrointestinal or dermatological side effects.^[1]

Efficacy and susceptibility

Cefodizime demonstrated superior clinical efficacy that what could be predicted from its in vitro experimental results. Certain immunomodulatory properties of the drug might account for its increased in vivo activity against specific bacterial species. These immunomodulatory properties stimulate some phagocyte and lymphocyte cellular functions when they have been impaired.^[1] It was shown in a 2004 study that cefodizime increased expression of toll-like receptor 4 (TLR-4) in neutrophils stimulated by Klebsiella pneumoniae infection which then affected the production of cytokines in the stimulated cells.^[2] A 1992 study conducted in vitro susceptibility studies for cefodizime and found that gram negative bacteria with consistent susceptibility include: Enterobacteriaceae including E. coli, Klebsiella pneumonia, Morganella morganii, Proteus mirabilis, P. vulgaris, Shigella sonnei, Yersinia enterocolitica, Salmonella, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Neisseria meningitidis. In vitro susceptible gram positive bacteria include: methicillin-sensitive Staphylococcus aureus, and Streptococcus agalactiae, S. pneumoniae and S. pyogenes. Cefodizime was shown to be ineffective in vitro against Enterobacter spp., Pseudomonas aeruginosa, and Xanthomonas maltophilia. Gram positive bacteria it was inactive against include Staphylococcus epidermidis and methicillin-resistant Streptococcus aureus. In this trial, bacteria were considered susceptible if 90% or more of the strains were inhibited by cefodizime concentrations of at least 8 mg/L in vitro.^[1]

Pharmacokinetics

Intramuscular cefodizime bioavailability ranges from 90% to 100%. It distributes into many tissues and is approximately 81% bound to plasma proteins, chiefly albumin. The drug reaches minimum inhibitory concentrations approximately 2–3 hours after administration, maintaining it for several hours afterwards. Clearance of cefodizime from the body is predominantly renal, with the majority of the drug excreted unchanged within the first 12 hours. More specifically, cefodizime is mainly cleared via glomerular filtration in the kidney, in addition to some tubular secretion. In patients with normal renal function, the terminal phase elimination half-life is approximately 3.5 hours.^[1]

Adverse effects

Cefodizime has been shown to be generally well tolerated in drug trials and its adverse effects are mainly gastrointestinal or dermatological. Gastrointestinal adverse effects were observed in 2.4% of patients during clinical trials and included: diarrhea, nausea, vomiting, and elevated transaminases. Allergic symptoms were observed in 1.1% of patients and include: exanthema, urticaria, and pruritus. Other adverse effects observed include local site reactions, pain at site of injection, and phlebitis.^[1]

Administration

Cefodizime is available as an intramuscular injection or as an intravenous bolus or infusion and is usually given 1 or 2 times a day. In clinical trials, the most frequently used adult dosages ranged from 2 grams to 4 grams IM or IV per day given as a single dose or in 2 divided doses.^[1]

References

^ ^a ^b ^c ^d ^e ^f Barradell, Lee B.; Brogden, Rex N. (1993). "Cefodizime: A Review of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Use". Drugs 44 (5): 800–834. doi:10.2165/00003495-199244050-00008. PMID 1280568. Retrieved 29 October 2014.
^ Song, H; Li, G; Ye, J; Qian, Y (2004). "Immunomodulating effects of cefodizime on Klebsiella pneumoniae-stimulated neutrophils.". Immunobiology 209 (3): 277–82. doi:10.1016/j.imbio.2004.05.003. PMID 15518339. Retrieved 1 November 2014.

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1. セフェム系 cephalosporins
2. セファロスポリン-アレルギー患者：セファロスポリンおよび関連抗菌薬のその後の使用 cephalosporin allergic patients subsequent use of cephalosporins and related antibiotics
3. セファロスポリンアレルギー：臨床症状および診断 cephalosporin allergy clinical manifestations and diagnosis
4. ペニシリン-アレルギー患者：セフェム系、カルバペネム系、およびモノバクタム系の使用 penicillin allergic patients use of cephalosporins carbapenems and monobactams
5. β-ラクタム系抗生物質：作用機序、耐性および有害作用 beta lactam antibiotics mechanisms of action and resistance and adverse effects

English Journal

Safety evaluation of cephalosporins based on utilization and adverse drug events: analysis of two databases in China.

Ren X, Liu D, Ding N, Huang K, Xiong Y, Du G, Zeng F.SourceHuazhong University of Science and Technology, Tongji Medical College, Tongji Hospital, Department of Pharmacy , 1095 Jiefang Road, Wuhan, Hubei Province, 430030, PR China.
Expert opinion on drug safety.Expert Opin Drug Saf.2012 Sep;11(5):689-97. doi: 10.1517/14740338.2012.699037. Epub 2012 Jun 19.
OBJECTIVE: The aim of this study is to evaluate the safety of cephalosporins, based on utilization and adverse drug events (ADEs).METHODS: This is a retrospective study using data on cephalosporins, obtained from Yangtze River hospital drug information and the Wuhan adverse drug reactions monitoring
PMID 22708900

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan.

Takahashi S, Kurimura Y, Hashimoto J, Uehara T, Hiyama Y, Iwasawa A, Nishimura M, Sunaoshi K, Takeda K, Suzuki N, Tsukamoto T.SourceDepartment of Urology, Sapporo Medical University School of Medicine, S. 1, W. 16 Chuo-ku, Sapporo, 0608543, Japan, stakahas@sapmed.ac.jp.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.J Infect Chemother.2012 Jul 14. [Epub ahead of print]
The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with o
PMID 22797875

Japanese Journal

Multiple doses of cefodizime are necessary for the treatment of Neisseria gonorrhoeae pharyngeal infection

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 12(3), 145-147, 2006-06-01
NAID 10017608133

Single dose of cefodizime completely eradicated multidrug-resistant strain of Neisseria gonorrhoeae in urethritis and uterine cervicitis

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 12(2), 97-99, 2006-04-01
NAID 10017421551

<I>Neisseria gonorrhoeae</I>に対するtelithromycinの<I>in vitro</I>抗菌力

The Japanese Journal of Antibiotics 58(3), 317-325, 2005
NAID 130004396017

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Cefodizime
Systematic (IUPAC) name
	(6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-; methoxyiminoacetyl]amino}-3-{[5-(carboxymethyl)-; 4-methyl-1,3-thiazol-2-yl]sulfanylmethyl}-8-oxo-; 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Identifiers
CAS Registry Number	69739-16-8
ATC code	J01DD09
PubChem	CID: 5361871
ChemSpider	4514859
UNII	Z31298J4HQ
KEGG	D07643
ChEMBL	CHEMBL1161746
Chemical data
Formula	C20H20N6O7S4
Molecular mass	584.673 g/mol
	SMILES O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=N\OC)/c3nc(sc3)N)CSc4nc(c(s4)CC(=O)O)C)C(=O)O;
	InChI InChI=1S/C20H20N6O7S4/c1-7-10(3-11(27)28)37-20(22-7)36-5-8-4-34-17-13(16(30)26(17)14(8)18(31)32)24-15(29)12(25-33-2)9-6-35-19(21)23-9/h6,13,17H,3-5H2,1-2H3,(H2,21,23)(H,24,29)(H,27,28)(H,31,32)/b25-12-/t13-,17-/m1/s1 ; Key:XDZKBRJLTGRPSS-BGZQYGJUSA-N ;
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