< 觀念剖析 >
Cephalosporin頭孢類藥物是一種殺菌藥(bactericidal)，正確名稱為Cephem類，抗菌機轉與青黴素類相同(have the same mode of action as other beta-lactam antibiotics)，它能與細菌細胞膜上的penicillin-binding proteins(PBPs)結合，阻止細菌細胞壁mucopeptide的合成，導致滲透不穩定的細胞壁(disrupt the synthesis of the peptidoglycan layer of bacterial cell walls)。
【註】 |
PBPs bind to the D-Ala-D-Ala at the end of mucopeptide to crosslink the peptidoglycan. β-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of peptidoglycan |
Cephalosporin類依其結構可區分為cephalosporin、cephamycin 兩類。此外，此類藥物可再依其抗菌範圍，區分第一代~第四代Cephalosporins，甚至第五代。
< 藥品分類 >
Cephalosporin 可分為如下：
第一代 Cephalosporin |
Cefacetrile、Cefadroxil (Duricef), Cephalexin (Keflex),, Cefaloridine, Cefalotin (Keflin), Cefapirin (Cefadryl), Cefazolin (Ancef, Kefzol), Cefradine (Velosef), Cefroxadine |
第二代 Cephalosporin |
Cefaclor (Ceclor , Keflor, Raniclor), Cefonicid (Monocid), Cefprozil (cefproxil; Cefzil), Cefuroxime (Zefu, Zinnat, Zinacef, Ceftin, Biofuroksym, Xorimax), Cefuzonam.
‧cephalosporins with antianaerobe activity: Cefmetazole, Cefotetan, Cefoxitin |
第三代 Cephalosporin |
Cefdinir (Zinir, Omnicef, Kefnir), Cefixime (Zifi, Suprax), Cefotaxime (Claforan), Cefovecin (Convenia),Cefpodoxime (Vantin, PECEF), Ceftibuten (Cedax), Ceftizoxime (Cefizox), Ceftriaxone (Rocephin).
‧cephalosporins with antipseudomonal activity: Cefoperazone (Cefobid), Ceftazidime (Fortum, Fortaz) |
第四代 Cephalosporin |
Cefclidine, Cefepime (Maxipime), Cefluprenam, Cefoselis, Cefozopran, Cefpirome (Cefrom), Cefquinome, flomoxef |
第五代 Cephalosporin |
Ceftobiprole, Ceftaroline |
< 抗菌範圍 >
1、第一代Cephalosporin： |
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(1) |
對G(+)菌的抗菌作用較第二代、第三代強。主要包括對MSSA及Streptococcus。對大部分簡單的G(-)細菌也有一點效果，但效果差，包括E. coli、Klebsiella、Proteus等。 |
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(2) |
能被細菌產生的β-內 胺 (β-lactamase)破壞，所以第一代cephalosporin對MRSA及Enterococcus 無效(No activity against methicillin-resistant staphylococci or enterococci)。 |
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(3) |
主要用於治療敏感菌所導致的URI及UTI、皮膚軟組織感染等。 |
Gram-positive: Activity against penicillinase- producing, methicillin-susceptible staphylococci and streptococci . No activity against methicillin-resistant staphylococci or enterococci
Gram-negative: Activity against Proteus mirabilis, some E. coli, and Klebsiella pneumoniae ("PEcK"), but have no activity against Bacteroides fragilis, Pseudomonas, Acinetobacter, Enterobacter, indole-positive Proteus, or Serratia. |
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2、第二代Cephalosporin： |
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(1) |
對G(+)菌的抗菌作用較第一代差，但對G(-)細菌的抗菌活性增加，包括對Proteus、E. coli、Klebsiella的效力比一代為佳，對H. influenzae也有效，對厭氧菌也有一定作 用，如Cefmetazole, Cefotetan, Cefoxitin；但對銅綠假單孢菌(Pseudomonas) 無效。 |
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(2) |
對多種細菌產生的β-內胺比較穩定。 |
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(3) |
主要用於治療敏感菌所導致Pneumonia、膽道感染、UTI、菌血症。 |
Gram-positive: Less than first-generation.
Gram-negative: Greater than first-generation: HEN (Haemophilus influenzae, Enterobacter aerogenes and some Neisseria + Proteus mirabilis, some E. coli, and Klebsiella pneumoniae |
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3、第三代Cephalosporin： |
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(1) |
具有更強對抗G(-)細菌的活性，包括對腸桿菌、厭氧菌等具有一定作用，對H. influenzae 也具有效力，但對MRSA及Enterococcus無效，對Streptococcus則仍有效力。第三代中的Ceftazidime具有抗pseudomonas的效果，而其它第三代cephalosporin 則無效。 |
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(2) |
對β-內胺有較高的穩定性。 |
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(3) |
主要用於治療危及生命的敗血症、腦膜炎(meningitis)、肺炎、骨髓炎、嚴重的UTI。 |
Gram-positive: Some members of this group (in particular, those available in an oral formulation, and those with anti-pseudomonal activity) have decreased activity against Gram-positive organisms.
Gram-negative: a broad spectrum of activity and further increased activity against Gram-negative organisms. They may be particularly useful in treating hospital-acquired infections. They are also able to penetrate the CNS, making them useful against meningitis caused by pneumococci, meningococci, H. influenzae, and susceptible E. coli, Klebsiella, and penicillin-resistant N. gonorrhoeae. Since 2007, ceftriaxone or cefixime have been the only recommended treatment for gonorrhea in the United States |
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4、第四代Cephalosporin： |
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(1) |
第四代對G(+)、G(-)菌均有效，它除了具有第三代的抗菌活性外，對MSSA也具有抗菌活性，對Pseudomonas也有效，但對MRSA及Enterococcus 仍無效。 |
Gram-positive: They are extended-spectrum agents with similar activity against Gram-positive organisms as first-generation cephalosporins.
Gram-negative: Fourth-generation cephalosporins are zwitterions that can penetrate the outer membrane of Gram-negative bacteria. They also have a greater resistance to beta-lactamases than the third-generation cephalosporins. Many can cross the blood-brain barrier and are effective in meningitis. They are also used against Pseudomonas aeruginosa. |
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5、第五代Cephalosporin：(這樣的分類還未被廣泛接受) |
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對抗Pseudomonas強效。 |
Ceftobiprole has been described as "fifth-generation" cephalosporin. though acceptance for this terminology is not universal. Ceftobiprole has powerful antipseudomonal characteristics and appears to be less susceptible to development of resistance. |
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< 代謝途徑 >
口服吸收良好，但吸收會受食物的干擾而延遲。靜脈注射的吸收不錯，血中尖峰藥物濃度通常為30min~60 min。大多數cephalosporin由腎臟排泄。當腎臟衰竭時，cephalosporin的排除半衰期會延長，對於腎功能不全的患者需調整劑量。
< 副作用>
口服偶有胃腸道方面反應，如食慾不振、噁心、腹痛、腹瀉、消化不良。靜脈給藥可發生靜脈炎。過敏反應包括皮疹、蕁麻疹、發燒，過敏性休克罕見，對青黴素過敏者約10%對cephalosporin過敏。血液學方面有嗜中性白血球↓，白血球↓，血小板↓。其它尚有頭痛、頭暈等CNS中毒反應、感覺異常等。另外，第一代cephalosporin大量使用時，可損害近曲小管而出現腎臟毒性。第四代cephalosporin幾乎無腎臟毒性。
(Common ADRs( 1% of patients) associated with the cephalosporin therapy include: diarrhea、nausea、rash、electrolyte disturbances、pain and inflammation at injection site。Infrequent ADRs (0.1~ 1% of patients) include: vomiting、headache、dizziness、oral and vaginal candidiasis、eosinophilia、 pseudomembranous colitis、superinfection、fever。The commonly quoted figure of 10% of patients with allergic hypersensitivity to penicillins。
(Several cephalosporins are associated with hypoprothrombinemia and a disulfiram-like reaction with ethanol。This is thought to be due to the N-methylthiotetrazole (NMTT) side-chain of these cephalosporins, which blocks the enzyme vitamin K epoxide reductase (likely causing hypothrombinemia) and aldehyde dehydrogenase (causing alcohol intolerance)。
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