現在位置 : 藥物 > 抗生素 賜復力生 Ceflexin - Cephalosporin
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抗生素 賜復力生膠囊 (５００公絲) (賜福力欣)
CEFLEXIN CAPSULES 500mg (CEPHALEXIN) "VPP" 頭孢菌素(Cephalosporin) 頭孢菌素(Cephalosporin)，又稱先鋒黴素，是一系列屬於β內醯胺類的抗生素。與頭黴素一併細分為頭孢烯。 頭孢菌素化合物最初是於1948年，由義大利科學家Giuseppe Brotzu從薩丁島排水溝中的頂頭孢提煉出來。他發現這些頂頭孢分泌出一些物質，可以有效抵抗引致傷寒的傷寒桿菌。牛津大學成功提煉出對β內醯胺酶穩定的頭孢菌素C，但卻未有足夠的效力作臨床使用。頭孢菌素的核心是7-氨基頭孢烯酸（簡稱7-ACA）是從頭孢菌素C中衍生出來，並已證實與青黴素的核心（即6-氨基青黴烷酸，6-APA）相似。對7-ACA的旁鏈作出修改，得出一些非常有用的抗生素，而第一種的頭孢噻吩便是由禮來公司於1964年發行。 作用反應模式 頭孢菌素能殺菌及與其他β內醯胺類抗生素（如青黴素）有相同的反應模式。頭孢菌素破壞細菌細胞壁肽聚糖的合成。肽聚糖對細菌，尤其是革蘭氏陽性菌細胞壁的結構完整性起著重要的作用。合成肽聚糖最後的步驟中是由轉肽酶（又稱為青黴素結合蛋白）所催化。 臨床使用 症狀 頭孢菌素是預防性質及用於治療細菌感染。第一代的頭孢菌素在抵抗革蘭氏陽性菌有出色的表現，而其後的頭孢菌素則增強對抗革蘭氏陰性菌，但是對革蘭氏陽性菌的抵抗力會相應下降。 副作用 頭孢菌素治療會引發的一般藥物不良反應（即多於1%的病人）包括腹瀉、反胃、皮疹、電解質不平衡，及／或在注射位置感到疼痛及發炎。不常出現的不良反應（即0.1-1%的病人）則包括嘔吐、頭痛、頭昏、口腔及陰道念珠菌病、假膜性結腸炎、二重感染、嗜酸細胞增多及／或發熱。少數甚至會發生過敏性休克。 約5-10%的對青黴素及／或碳青黴烯過敏的病人，會同樣對頭孢菌素過敏。所以若病人對它們曾有過敏的紀錄，如蕁麻疹、過敏反應、間質腎炎等，使用這些抗生素是一種禁忌。 分類 頭孢菌素核心能作出不同的修改以達至不同的特性。頭孢菌素是以它們的抗菌特性來分類。最初的頭孢菌素被命名為第一代,而其後的則分為第二代。每一代新的系列都有著對革蘭氏陰性菌較上一代顯著的抗菌性，但在某些品種上卻對革蘭氏陽性菌降低了抗菌性。第四代的頭孢菌素則有著廣泛的效力。 雖然這樣的分類方法並不怎麼準確，但卻是現時最普遍的分類法。例如，在日本並未為頭孢菌素分類第四代，但卻仍然將頭孢克洛分類為第一代；頭孢拉宗、頭孢米諾及頭孢替坦分類為第二代。頭孢烯；頭孢美唑及頭孢西丁分類為第三代頭孢烯類抗生素；而氟氧頭孢、拉氧頭孢則分類為氧頭孢烯。 大部份第一代的頭孢菌素的英文是以「ceph-」開首，尤其是北美洲及澳大利亞等國家。歐洲則以「cef-」為開首，較新的第一代頭孢菌素及其後的世代都是以此為開首的。 第一代 第一代頭孢菌素是較溫和的抗生素，能抵抗包括能生產青黴素酶及敏感甲氧西林的葡萄球菌屬及鏈球菌等細菌，縱然它們不是這種細菌感染的首選治療藥物。它們另外亦會抵抗一些大腸桿菌、克雷白氏肺炎桿菌及奇異變型桿菌，但對脆弱擬桿菌、腸球菌、抗藥性葡萄球菌、假單胞菌屬、不動桿菌屬、腸桿菌屬、引朵陽性變型桿菌或沙雷氏菌沒有功效。 第一代頭孢菌素包括： 頭孢氰甲 頭孢羥氨芐（Cefadroxil、Duricef®） 頭孢氨芐（Keflex®） 頭孢來星 頭孢洛寧 頭孢噻啶 頭孢噻吩（Keflin®） 頭孢匹林（Cefapirin、Cefadryl®） 頭孢曲秦（Cefatrizine） 頭孢氮氟 頭孢西酮 頭孢唑林（Ancef®、Kefzol®） 頭孢拉定（Cefadine、Velosef®） 頭孢沙定 頭孢替唑 第二代 第二代頭孢菌素有較大的革蘭氏陰性菌的抗菌性，且保留一些革蘭氏陽性菌的抗菌性。它們對β內醯胺酶有更大的抵抗力。 頭孢克洛（Ceclor®） 頭孢尼西（Monocid®） 頭孢丙烯（Cefzil®） 頭孢呋辛（Zinnat®、Zinacef®、Ceftin®） 頭孢唑南（Cefuzonam） 第二代頭孢菌素有著抗厭氧性生物性的包括： 頭孢孟多（Cefamandole） 頭孢雷特 頭孢替安（Cefotiam） 以下的頭孢烯有時亦被分類為第二代頭孢菌素： 碳頭孢烯：氯碳頭孢（Lorabid®） 頭黴素：頭孢拉宗、頭孢美唑（Cefmetazole、Zefazone®）、頭孢米諾（Cefminox）、頭孢替坦（Cefotetan、Cefotan®）、頭孢西丁（Cefoxitin、Mefoxin®） 第三代 第三代的頭孢菌素有廣泛的抗菌性，且增加了抵抗革蘭氏陰性菌的能力。某些頭孢菌素，尤其是口服的及具抗假單胞菌屬能力的，對革蘭氏陽性菌有減少了的抗菌性。雖然擴展了的藥性，β內醯胺酶使得它們在臨床的用途減少，但它們仍特別適用於治療院內感染。 頭孢卡品 頭孢達肟 頭孢地尼（Cefdinir、Omnicef®） 頭孢托侖 頭孢他美 頭孢克肟（Suprax®） 頭孢甲肟 頭孢地秦〈Cefodizime〉 頭孢哌酮（Cefobid®） 頭孢噻肟（Claforan®） 頭孢咪唑 頭孢泊肟（Vantin®） 頭孢特侖（Cefteram） 頭孢布烯（Ceftibuten、Cedax®） 頭孢噻呋 頭孢噻林 頭孢唑肟（Cefizax®） 頭孢曲松（羅氏芬®） 以下是有著抵抗假單胞菌屬能力的第三代頭孢菌素： 頭孢他啶（覆達欣®、Fortaz®） 頭孢匹胺 頭孢磺啶 以下的頭孢烯有時亦被分類為第三代頭孢菌素： 氧頭孢烯：拉氧頭孢（Latamoxef sodium） 第四代 第四代頭孢菌素與第一代在對革蘭氏陽性菌有相似的抗菌性，但它的抗菌性則更廣泛。它們相比第三代有更強的對β內醯胺酶的抵抗力。大部份能穿透腦血管障壁及對治療腦膜炎十分有效。 Cefclidine 頭孢吡肟（Maxipime®） 頭孢瑞南 頭孢噻利 頭孢唑蘭 頭孢匹羅（Cefpirome） 頭孢喹肟 以下的頭黴素有時亦被分類為第四代頭孢菌素： 氧頭孢烯：氟氧頭孢（Flomoxef） |
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DOSAGE AND ADMINISTRATION:
Usual Adult Dosage: Type of Infection Dose / Frequency Moderate to severe infections 500 mg to 1 gram every 6 to 8 hrs. Mild infections caused by susceptible gram-positive cocci 250 mg to 500 mg every 8 hours Acute, uncomplicated urinary tract infections 1 gram every 12 hours Pneumococcal pneumonia 500 mg every 12 hours Severe, life-threatening infections (e.g., endocarditis, septicemia)* 1 gram to 1.5 grams every 6 hours *In rare instances, doses of up to 12 grams of Cefazolin Injection per day have been used. Perioperative Prophylactic Use To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are: 1. 1 gram IV administered one-half hour to 1 hour prior to start of surgery. 2. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV during surgery (administration modified depending on the duration of the operative procedure). 3. 500 mg to 1 gram IV every 6 to 8 hours for 24 hours postoperatively. It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior to start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision; and (2) cefazolin be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms. In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin may be continued for 3 to 5 days following the completion of surgery. Renal Dosing: ------------------------ Cefazolin Injection may be used in patients with reduced renal function with the following dosage adjustments: Patients with a creatinine clearance of 55 mL/min. or greater or a serum creatinine of 1.5 mg % or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3.0 mg % can also be given full doses but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine of 3.1 to 4.5 mg % should be given one-half the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min. or less or serum creatinine of 4.6 mg % or greater should be given ½ the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. |
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Cephalosporins
The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as "Cephalosporium". Together with cephamycins, they constitute a subgroup of β-lactam antibiotics called cephems. Cephalosporins were discovered in 1945 and were first sold in 1964. Medical Uses Cephalosporins are indicated for the prophylaxis and treatment of infections caused by bacteria susceptible to this particular form of antibiotic. First-generation cephalosporins are active predominantly against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria (albeit often with reduced activity against Gram-positive organisms). Adverse Effects Common adverse drug reactions (ADRs) (≥ 1% of patients) associated with the cephalosporin therapy include: diarrhea, nausea, rash, electrolyte disturbances, and pain and inflammation at injection site. Infrequent ADRs (0.1–1% of patients) include vomiting, headache, dizziness, oral and vaginal candidiasis, pseudomembranous colitis, superinfection, eosinophilia, nephrotoxicity, neutropenia, thrombocytopenia, and fever. The commonly quoted figure of 10% of patients with allergic hypersensitivity to penicillins and/or carbapenems also having cross-reactivity with cephalosporins originated from a 1975 study looking at the original cephalosporins, and subsequent "safety first" policy meant this was widely quoted and assumed to apply to all members of the group. Hence, it was commonly stated that they are contraindicated in patients with a history of severe, immediate allergic reactions (urticaria, anaphylaxis, interstitial nephritis, etc.) to penicillins, carbapenems, or cephalosporins. This, however, should be viewed in the light of recent epidemiological work suggesting, for many second-generation (or later) cephalosporins, the cross-reactivity rate with penicillin is much lower, having no significantly increased risk of reactivity over the first generation based on the studies examined. The British National Formulary previously issued blanket warnings of 10% cross-reactivity, but, since the September 2008 edition, suggests, in the absence of suitable alternatives, oral cefixime or cefuroxime and injectable cefotaxime, ceftazidine, and ceftriaxone can be used with caution, but the use of cefaclor, cefadrocil, cefalexin, and cefradine should be avoided. Overall, the research shows that all beta lactams have the intrinsic hazard of very serious hazardous reactions in susceptible patients. Only the frequency of these reactions vary, based on the structure. Recent papers have shown that a major feature in determining frequency of immunological reactions is the similarity of the side chains (e.g., first generation cephalosporins are similar to penicillins), and this is the reason the β-lactams are associated with different frequencies of serious reactions (e.g., anaphylaxis). Several cephalosporins are associated with hypoprothrombinemia and a disulfiram-like reaction with ethanol. These include latamoxef, cefmenoxime, moxalactam, cefoperazone, cefamandole, cefmetazole, and cefotetan. This is thought to be due to the N-methylthiotetrazole side-chain of these cephalosporins, which blocks the enzyme vitamin K epoxide reductase (likely causing hypothrombinemia) and aldehyde dehydrogenase (causing alcohol intolerance). Mechanism of Action Cephalosporins are bactericidal and have the same mode of action as other β-lactam antibiotics (such as penicillins), but are less susceptible to β-lactamases. Cephalosporins disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. The peptidoglycan layer is important for cell wall structural integrity. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases[disambiguation needed] known as penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby irreversibly inhibiting PBP crosslinking of peptidoglycan. Resistance Resistance to cephalosporin antibiotics can involve either reduced affinity of existing PBP components or the acquisition of a supplementary β-lactam-insensitive PBP. Currently, some Citrobacter freundii, Enterobacter cloacae, Neisseria gonorrhoeae, and Escherichia coli strains are resistant to cephalosporins. Some Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, and Serratia marcescens strains have also developed resistance to cephalosporins to varying degrees. Classification The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are sometimes grouped into "generations" by their antimicrobial properties. The first cephalosporins were designated first-generation cephalosporins, whereas, later, more extended-spectrum cephalosporins were classified as second-generation cephalosporins. Each newer generation has significantly greater Gram-negative antimicrobial properties than the preceding generation, in most cases with decreased activity against Gram-positive organisms. Fourth-generation cephalosporins, however, have true broad-spectrum activity. The classification of cephalosporins into "generations" is commonly practised, although the exact categorization is often imprecise. For example, the fourth generation of cephalosporins is not recognized as such in Japan.[citation needed] In Japan, cefaclor is classed as a first-generation cephalosporin, though in the United States it is a second-generation one; and cefbuperazone, cefminox, and cefotetan are classed as second-generation cephalosporins. Cefmetazole and cefoxitin are classed as third-generation cephems. Flomoxef and latamoxef are in a new class called oxacephems. Most first-generation cephalosporins were originally spelled "ceph-" in English-speaking countries. This continues to be the preferred spelling in the United States, Australia, and New Zealand, while European countries (including the United Kingdom) have adopted the International Nonproprietary Names, which are always spelled "cef-". Newer first-generation cephalosporins and all cephalosporins of later generations are spelled "cef-", even in the United States. Some state that cephalosporins can be divided into five or even six generations, although the usefulness of this organization system is of limited clinical relevance. Fourth-generation cephalosporins as of March, 2007, were considered to be "a class of highly potent antibiotics that are among medicine's last defenses against several serious human infections" according to the Washington Post. The mnemonic "LAME" is used to note organisms against which cephalosporins do not have activity: Listeria, Atypicals (including Mycoplasma and Chlamydia), MRSA, and enterococci. Fifth-generation cephalosporins are effective against MRSA, however. |
