与β-内酰胺类抗生素相关的中性粒细胞减少症。

Kirkwood C F, Smith L L, Rustagi P K, Schentag J J

Clin Pharm. 1983 Nov-Dec;2(6):569-78.

Two patients who developed neutropenia while receiving beta-lactam antibiotics are presented, and the literature on beta-lactam-induced neutropenia is reviewed. A 55-year-old white woman was admitted to the hospital with a white blood cell (WBC) count of 8700/cu mm (68% neutrophils, 12% neutrophil bands, 0% eosinophils, 14% lymphocytes, 5% monocytes). Moxalactam 2 g i.v. (as the disodium salt) every eight hours was started on hospital day 15 after a postoperative fever failed to respond to a regimen of intravenous tobramycin and clindamycin. The patient again had surgery on hospital day 27, and the moxalactam regimen was continued postoperatively. Approximately one week later the patient's WBC count had dropped to 1900/cu mm (8% neutrophils, 14% neutrophil bands, 6% eosinophils, 54% lymphocytes, 16% monocytes); moxalactam was discontinued, and the WBC count gradually increased after substitution of tobramycin and clindamycin for moxalactam. The second patient was a 75-year-old white man who was being treated with intravenous tobramycin and cefoxitin for a hospital-acquired pneumonia. Ticarcillin 3 g i.v. (as the disodium salt) every four hours was added to this regimen on hospital day 23 after sputum cultures revealed Pseudomonas aeruginosa; four days previously, the WBC count had been 25,100/cu mm (64% neutrophils, 31% neutrophil bands, 1% eosinophils, 3% lymphocytes, 0% monocytes). The WBC count on hospital day 36 was 11,900/cu mm (39% neutrophils, 33% neutrophil bands, 11% eosinophils, 10% lymphocytes, 6% monocytes). Two days later it had dropped to 3700/cu mm (2% neutrophils, 0% neutrophil bands, 53% eosinophils, 24% lymphocytes, 16% monocytes), and ticarcillin was discontinued. The WBC count gradually increased and returned to normal within three days after discontinuing ticarcillin. Neutropenia associated with the administration of beta-lactam antibiotics appears to result from an immunologic reaction characterized by rapid destruction of peripheral neutrophils. Among penicillin analogs, penicillinase-resistant penicillins are involved most frequently, especially in pediatric patients receiving dosages of 150 mg/kg/day or greater. Two case reports have implicated ticarcillin as a cause of neutropenia; moxalactam has not been associated with this adverse effect in previous literature reports. Discontinuation of the suspected agent and initiation of an alternative antibiotic regimen is recommended as initial treatment of this condition since recovery usually occurs within days after discontinuing the offending drug.

本文报告了2例在接受β-内酰胺类抗生素治疗时发生中性粒细胞减少的患者，并对β-内酰胺类抗生素所致中性粒细胞减少的相关文献进行了综述。1例55岁白人女性因白细胞（WBC）计数8700/立方毫米（中性粒细胞68%，中性粒细胞杆状核12%，嗜酸性粒细胞0%，淋巴细胞14%，单核细胞5%）入院。术后发热对静脉注射妥布霉素和克林霉素治疗方案无反应，于住院第15天开始每8小时静脉注射2克拉氧头孢（作为二钠盐）。患者于住院第27天再次接受手术，术后继续使用拉氧头孢治疗方案。大约一周后，患者的WBC计数降至1900/立方毫米（中性粒细胞8%，中性粒细胞杆状核14%，嗜酸性粒细胞6%，淋巴细胞54%，单核细胞16%）；停用拉氧头孢，用妥布霉素和克林霉素替代拉氧头孢后，WBC计数逐渐升高。第2例患者为75岁白人男性，因医院获得性肺炎接受静脉注射妥布霉素和头孢西丁治疗。痰培养显示铜绿假单胞菌后，于住院第23天在此治疗方案中加入每4小时静脉注射3克替卡西林（作为二钠盐）；4天前，WBC计数为25100/立方毫米（中性粒细胞64%，中性粒细胞杆状核31%，嗜酸性粒细胞1%，淋巴细胞3%，单核细胞0%）。住院第36天WBC计数为11900/立方毫米（中性粒细胞39%，中性粒细胞杆状核33%，嗜酸性粒细胞11%，淋巴细胞10%，单核细胞6%）。两天后降至3700/立方毫米（中性粒细胞2%，中性粒细胞杆状核0%，嗜酸性粒细胞53%，淋巴细胞24%，单核细胞16%），停用替卡西林。停用替卡西林后3天内WBC计数逐渐升高并恢复正常。与β-内酰胺类抗生素给药相关的中性粒细胞减少似乎是由一种免疫反应引起的，其特征是外周中性粒细胞迅速被破坏。在青霉素类似物中，耐青霉素酶的青霉素最常涉及，尤其是在接受每日剂量150毫克/千克或更高剂量的儿科患者中。有2例报告提示替卡西林是中性粒细胞减少的原因；在以往的文献报告中，拉氧头孢未与这种不良反应相关。建议停用可疑药物并开始使用替代抗生素治疗方案作为该病的初始治疗，因为停药后通常在数天内即可恢复。