快樂小藥師 Im pharmacist nichts glücklich

之前有人問我一個問題：tetracycline會和penicillin因為交互作用減少penicillin的效果，那為何結構相似的cephalosporin卻沒有在交互作用的名單裡面呢？

 其實，我也不知道。

 從lexicomp的資料可以得知：

或是妳從Micromedex也可以查到一樣的資料：

Warning:

Concurrent use of PENICILLIN and TETRACYCLINES may result in decreased antibacterial effectiveness.

Clinical Management:

Monitor signs of antibacterial effectiveness.

Onset:

Delayed

Severity:

Moderate

Documentation:

Good

Probable Mechanism:

decreased bactericidal activity

Summary:

Bacteriostatic drugs, such as the tetracyclines, may interfere with the bactericidal effect of penicillin (Moellering, 1983). Such concomitant use should be avoided (Prod Info DYNACIN® oral tablets, 2003).

Literature:

In a review of 43 adult patients seen in one medical facility during 1950 to 1960 with a diagnosis of pneumococcal meningitis, 7 received treatment with penicillin plus a tetracycline. Of these 7 patients, 6 died (mortality of 85%). While not the only contributing factor in the clinical outcome of these patients, the antibiotic antagonism is worth noting (Olsson et al, 1961).

Reference(s):

Moellering RC: Rationale for use of antimicrobial combinations. Am J Med 08/29/1983; 75(2A):4-8.

Olsson RA: Pneumococcal meningitis in the adult. Clinical, therapeutic, and prognostic aspects in forty-three patients. Ann Intern Med 10/00/1961; 55:545-549.

Product Information: DYNACIN(R) oral tablets, minocycline hcl oral tablets. MEDICIS Pharmaceutical Corp., Scottsdale, AZ, 10/00/2003.

從結構上面來看：

tetracycline:

Penicillin:

Cephalosporin:

確實結構上來說，penicillin和cephalosporin是相近的，但是引起治療效果減低的原因，並不是在結構的衝突上面，是在對細菌的作用上面，簡單的說，就是藥理上的衝突（抑菌和殺菌併用時的干擾問題），所以目前為止，用結構來說tetracyclin會影響cephalosporin的藥效似乎不是這樣適當。

為了更近一步了解真相，所以我就寫信去問約翰霍普金斯大學的教授，Paul Pham, PharmD回信跟我說：

When penicillin is used in combination with tetracyclines, the bactericidal effect of penicillins may be diminished in vivo. In two studies involving a total of 79 patients with pneumococcal meningitis treated with either penicillin plus tetracyclines or penicillin monotherapy resulted in a higher mortality rate (79-85%) in the combination therapy compared to penicillin monotherapy (30-33%) [Arch Intern Med 1951:88:489;Ann Intern Med 1961; 55:545]. However there no difference in mortality was observed when penicillin was used in combination with tetracycline for the treatment of pneumococcal pneumonia [Arch Intern Med 1953; 91:197]. The exact mechanism diminished bacterial cidal effect with the combination is not well understood, but may secondary to decreased penicillin binding protein when tetracycline is co-administered. No data is available with cephalosporins, but a similar interaction is possible when cephalosporins are used for the treatment of meningitis.

換句話說，目前資料不足，所以也沒有辦法確定tetracycline和cephalosporins是不是真的沒有交互作用，但是也有可能是一種情形，就是其實也沒有必要在治療上面同時會用到這兩種抗生素，畢竟在腦膜炎的治療上面，頭孢菌素並不是主要的選擇，所以其實也不會發生這樣的事情。