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Claforan, Cefotaxime sodium

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/08 15:25:43」(JST)

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Cefotaxime

Systematic (IUPAC) name
(6R,7R,Z)-3-(Acetoxymethyl)-7-(2-(2-aminothiazol-4-yl)-2-(methoxyimino)acetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Clinical data
Trade names	Claforan ; Cefatam (LGls)
AHFS/Drugs.com	monograph
MedlinePlus	a682765
Pregnancy cat.	B1 (AU) B (US)
Legal status	Prescription Only (S4) (AU)
Routes	Intravenous and Intramuscular
Pharmacokinetic data
Bioavailability	n/a
Metabolism	Hepatic
Half-life	0.8–1.4 hours
Excretion	50–85% renal
Identifiers
CAS number	63527-52-6 Y
ATC code	J01DD01
PubChem	CID 5479527
DrugBank	DB00493
ChemSpider	4586392 Y
UNII	N2GI8B1GK7 Y
KEGG	D07647 Y
ChEMBL	CHEMBL102 Y
Chemical data
Formula	C16H17N5O7S2
Mol. mass	455.47 g/mol
SMILES O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)C(=N\OC)\c3nc(sc3)N)COC(=O)C)C(=O)O
InChI InChI=1S/C16H17N5O7S2/c1-6(22)28-3-7-4-29-14-10(13(24)21(14)11(7)15(25)26)19-12(23)9(20-27-2)8-5-30-16(17)18-8/h5,10,14H,3-4H2,1-2H3,(H2,17,18)(H,19,23)(H,25,26)/b20-9+/t10-,14-/m1/s1 Y Key:GPRBEKHLDVQUJE-VINNURBNSA-N Y
Y (what is this?)  (verify)

Cefotaxime (INN) /ˌsɛfɵˈtæksiːm/ is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, cefotaxime is a broad spectrum antibiotic with activity against numerous Gram positive and Gram negative bacteria.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.

Medical uses

Given its broad spectrum of activity, cefotaxime is used for a variety of infections, including:

• Lower respiratory tract infections - e.g. pneumonia (most commonly caused by S. pneumoniae).
• Genitourinary system infections - urinary tract infections (e.g. E. coli, S. epidermidis, P. mirabilis) and cervical/urethral gonorrhea.
• Gynecologic infections - e.g. pelvic inflammatory disease, endometritis, and pelvic cellulitis.
• Bacteremia/Septicemia - secondary to Streptococcus spp, S. aureus, E. coli, and Klebsiella spp.
• Intra-abdominal infections - e.g. peritonitis
• Bone and join infections - S. aureus, Streptococcus spp.
• CNS infections - e.g. meningitis/ventriculitis secondary to N. meningitidis, H. influenzae, S. pneumoniae.

Although cefotaxime has demonstrated efficacy in the preceding infections, this does not imply that it is considered to be the first-line agent. In meningitis, cefotaxime crosses the blood–brain barrier better than cefuroxime.

Vial of cefotaxime

Spectrum of activity

As a β-lactam antibiotic in the third-generation class of cephalosporins, cefotaxime is active against numerous gram-positive and gram-negative bacteria, including several with resistance to classic β-lactams such as penicillin. These bacteria often manifest as infections of the lower respiratory tract, skin, central nervous system (CNS), bone, and intra-abdominal cavity. While regional susceptibilities must always be considered, cefotaxime typically is effective against the following organisms (in addition to many others):

• Staphylococcus aureus (not including MRSA) and S. epidermidis
• Streptococcus pneumoniae and S. pyogenes
• Escherichia coli
• Haemophilus influenzae
• Neisseria gonorrhoeae and N. meningitidis
• Klebsiella spp
• Proteus mirabilis and P. vulgaris
• Enterobacter spp.
• Bacteroides spp.
• Fusobacterium spp.

Notable organisms against which cefotaxime is not active include Pseudomonas and Enterococcus. As listed, it has modest activity against the anaerobic Bacteroides fragilis.

The following represents MIC susceptibility data for a few medically significant microorganisms.

• Haemophilus influenzae: ≤0.007 µg/mL - 0.5 µg/mL
• Staphylococcus aureus: 0.781 µg/mL - 172 µg/mL
• Streptococcus pneumoniae: ≤0.007 µg/mL － 8 µg/mL

Historically, cefotaxime has been considered to be comparable to ceftriaxone (another third-generation cephalosporin) in safety and efficacy for the treatment of bacterial meningitis, lower respiratory tract infections, skin and soft tissue infections, genitourinary tract infections, bloodstream infections, as well as prophylaxis for abdominal surgery. The majority of these infections are caused by organisms traditionally sensitive to both cephalosporins. However, ceftriaxone has the advantage of once daily dosing, whereas the shorter half-life of cefotaxime necessitates two or three daily doses for efficacy. Changing patterns in microbial resistance suggest that cefotaxime may be suffering greater resistance than ceftriaxone, whereas the two were previously considered comparable. It is also important to consider regional microbial sensitivities when choosing any antimicrobial agent for the treatment of infection.

Adverse reactions

Cefotaxime is contraindicated in patients with a known hypersensitivity to cefotaxime or other cephalosporins. Caution should be used and risks weighed against potential benefits in patients with an allergy to penicillin, due to cross-reactivity between the classes.

The most common adverse reactions experienced are:

• Pain and inflammation at the site of injection/infusion (4.3%)
• Rash, pruritus, or fever (2.4%)
• Colitis, diarrhea, nausea, vomiting (1.4%)

Mechanism of action

Cefotaxime is a β-lactam antibiotic (which refers to the structural components of the drug molecule itself). As a class, β-lactams inhibit bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs). This inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) in the absence of cell wall assembly. Due to the mechanism of its attack on bacterial cell wall synthesis, β-lactams are considered to be bactericidal.

Unlike β-lactams such as penicillin and amoxicillin—which are highly susceptible to degradation by β-lactamase enzymes (produced, for example, nearly universally by Staphylococcus aureus)--cefotaxime boasts the additional benefit of resistance to β-lactamase degradation. This characteristic is due to the structural configuration of the cefotaxime molecule. The syn-configuration of the methoxyimino moiety confers stability against β-lactamase enzymes. Consequently, the spectrum of activity is broadened to include several β-lactamse producing organisms (which would otherwise be resistant to β-lactam antibiotics), as outlined below.

Cefotaxime, like other β-lactam antibiotics, does not only block the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the Glaucophytes, and the division of chloroplasts of bryophytes. In contrast, it has no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory and indicates an evolution of plastid division in land plants.

Administration

Cefotaxime is administered by intramuscular (I.M.) injection or intravenous (I.V.) infusion.

As cefotaxime is metabolized to both active and inactive metabolites by the liver and largely excreted in the urine, dose adjustments may be appropriate in people with renal or hepatic impairment.

Plant tissue culture

Cefotaxime is the only cephalosporin which has very low toxicity in plants, even at higher concentration (up to 500 mg/L). It is widely used to treat plant tissue infections with Gram negative bacteria, while vancomycin is used to treat the plant tissue infections with Gram positive bacteria.

References

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• 1. 頭蓋内硬膜外膿瘍 intracranial epidural abscess
• 2. 新生児の黄色ブドウ球菌やレンサ球菌による皮膚・軟部組織感染症の疑い：評価およびマネージメント suspected staphylococcus aureus and streptococcal skin and soft tissue infections in neonates evaluation and management
• 3. 新生児における細菌性髄膜炎：治療および転帰 bacterial meningitis in the neonate treatment and outcome
• 4. 成人における確定診断を得られていない低血圧やショックの評価および初期アプローチ evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock
• 5. セフェム系 cephalosporins

English Journal

• Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug-Resistant CTX-M-Producing Bacterial Pathogens.

• Shaikh S1, Rizvi SMD2, Shakil S3,4, Hussain T2, Alshammari TM5,6, Ahmad W3, Tabrez S7, Al-Qahtani MH3, Abuzenadah AM3,4.
• Journal of cellular biochemistry.J Cell Biochem.2017 Sep;118(9):2802-2808. doi: 10.1002/jcb.25929. Epub 2017 Apr 27.
• PMID 28181300

• Detection of molecular changes induced by antibiotics in Escherichia coli using vibrational spectroscopy.

• Xuan Nguyen NT1, Sarter S2, Hai Nguyen N3, Daniel P4.
• Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2017 Aug 5;183:395-401. doi: 10.1016/j.saa.2017.04.077. Epub 2017 Apr 27.
• PMID 28463778

• Mixed Micelles Loaded with Bile Salt: An Approach to Enhance Intestinal Transport of the BCS Class III Drug Cefotaxime in Rats.

• Arafat M1, Kirchhoefer C2, Mikov M3.
• European journal of drug metabolism and pharmacokinetics.Eur J Drug Metab Pharmacokinet.2017 Aug;42(4):635-645. doi: 10.1007/s13318-016-0375-9.
• PMID 27686853

Japanese Journal

• Development of Simple and Efficient in Planta Transformation Method for Wheat (Triticum aestivum L.) Using Agrobacterium tumefaciens(PLANT BIOTECHNOLOGY)

• Supartana Putu,Shimizu Tsutomu,Nogawa Masahiro,Shioiri Hidenari,Nakajima Tadashi,Haramoto Naoyuki,Nozue Masayuki,Kojima Mineo
• Journal of bioscience and bioengineering 102(3), 162-170, 2006-09-25
• … The inoculated seeds were incubated at 22℃ for 2 d and sterilized by cefotaxime (Claforan) (1000ppm water solution) treatment and then vernalized at 5℃ for 25 d. …
• NAID 110004809587

• 青枯病(Pseudomonas solanacearum)抵抗性付与のための抗細菌性遺伝子のAgrobacterium法による4倍体バレイショ品種への形質転換

• 渡邉 和男,Zambrano V.,Benavides J. [他]
• 近畿大学生物理工学研究所紀要 (3), 10-18, 2000-01
• … Hairy roots obtained were cultured in MS medium with Claforan then, in a regeneration medium containing 100ppm kanamycin. …
• NAID 120002246787

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