小龍醫師館

認識Cephalosporin

　　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。 　　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

1. 第一代Cephalosporin：
   (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。
   (2) 能被細菌產生的β-內 酰胺酶 (β-lactamase)破壞，所以第一代cephalosporin對MRSA及Enterococcus 無效(No activity against methicillin-resistant staphylococci or enterococci)。
   (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.

2. 第二代Cephalosporin：
   (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。
   (2) 對多種細菌產生的β-內酰胺酶比較穩定。
   (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

3. 第三代Cephalosporin：
   (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。
   (2) 對β-內酰胺酶有較高的穩定性。
   (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

4. 第四代Cephalosporin：
   (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.

5. 第五代Cephalosporin：(這樣的分類還未被廣泛接受)
   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.

　　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。
　　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)。

Cephalosporin、Cephem類、頭孢類藥物、青黴素類、皮膚軟組織感染、敏感菌、基礎醫學資訊館