1例头孢克洛致急性胆汁淤积型药物性肝损伤儿童患者的药学监护

1例11岁儿童患者,因服用头孢克洛4 d后出现尿黄、皮肤瘙痒入院。查肝功能异常,诊断为急性胆汁淤积型药物性肝损伤,给予保肝、退黄、降酶等对症治疗。针对患者未成年和肝损伤急性加重等特点,药学监护集中于保肝药物的合理选用、糖皮质激素个体化给药方案的制定、不良反应的监测以及药物不良相互作用的干预,同时通过用药教育提高患者用药依从性,减少潜在的用药风险。治疗4周后,患者肝功能恢复正常出院。     

Pharmacodynamic Activity of Five Oral Cephalosporins Against Haemophilus influenzae

Study Objectives . To determine the time above minimum inhibitory concentration (T > MIC) and serum bactericidal activity of five oral cephalosporins against two strains of Haemophilus influenzae. Design . Randomized, crossover study. Setting . University-associated research center. Subjects . Ten healthy volunteers. Interventions . Each subject received a single dose of cefpodoxime 200 mg, cefuroxime 500 mg, cefaclor 500 mg, cefprozil 500 mg, or loracarbef 400 mg each week for 5 weeks. Blood for serum levels was obtained at time zero and 1, 2, 3, 4, 6, 8, and 12 hours after each dose. Measurements and Main Results . Cefopodoxime produced serum concentrations above the MIC for more than 90% of the time for both β-lactamase-negative and -positive strains of H. influenzae. Moreover, it had serum bactericidal activity for 12 hours against both isolates. Cefuroxime was the second most active cephalosporin, with serum concentrations above the MIC of both isolates for 60% of the time. Cefuroxime provided serum bactericidal activity for 12 hours against the β-lactamase-negative strain and 6 hours against the β-lactamase-positive strain of H. influenzae. Even though the T > MIC was less than 50% of the study period for the other cephalosporins, all but cefaclor provided serum bactericidal activity for 12 hours against the β-lactamase-negative isolate. Cefaclor provided measurable serum bactericidal activity for only 3 hours. The duration of serum bactericidal activity of cefprozil, loracarbef, and cefaclor against the β-lactamase-positive isolate was 4, 2, and 0 hours, respectively. Conclusion . Cefpodoxime was the most active cephalosporin studied based on T > MIC and serum bactericidal activity against isolates of H. influenzae.     

头孢克洛胶囊治疗尿路感染临床研究

目的 研究头孢克洛胶囊治疗尿路感染的临床疗效。方法 治疗组62例尿路感染患者给予头孢克洛胶囊0．5g，每日3次口服，疗程7d；对照组58例尿路感染患者给予乳酸左氧氟沙星片0．1g，每日2次口服，疗程7d。观察两组患者症状、体征及实验室检查。结果 治疗组治疗后总有效率为95．2％，对照组治疗后总有效率为74．1％。结论 用头孢克洛胶囊治疗尿路感染安全有效．疗效明显优于对照组。     

The pharmacokinetics of the oral cephalosporins cefaclor, cephradine and cephalexin.

The pharmacokinetics of the oral cephalosporins cefaclor, cephradine, and cephalexin were examined following single 500 mg oral doses to fasted, healthy volunteers. Absorption of the three compounds was rapid following a brief lag period and peak serum levels were obtained in 1-1.5 hours. Serum levels of cefaclor tended to be lower than those of cephradine and cephalexin during the 2-5 hour postdosing period and cefaclor was eliminated more rapidly than other cephalosporins from serum. No difference was observed in the overall bioavailability of the three antibiotics based on comparable FD/V values. Urine levels of the three cephalosporins greatly exceeded the minimum inhibitory concentrations of susceptible organisms during 0-6 hours postdosing, but were considerably reduced during the 6-12 hour collection period. Total urinary recovery of antibiotic activity accounted for almost 90 percent of dosed cephradine and cephalexin compared to 55 percent of dosed cefaclor. Lower serum levels and reduced urinary recovery of intact cefaclor are probably due primarily to its chemical instability. The reduced levels of cefaclor may be compensated for therapeutically by its greater in vitro antibacterial activity.     

Comparative Pharmacokinetics of Oral Ceftibuten,Cefixime, Cefaclor,and Cefuroxime Axetil in Healthy Volunteers

Study Objective . To compare the pharmacokinetics of ceftibuten, cefixime, cefuroxime axetil, and cefaclor after oral administration. Design . Randomized, four-period, crossover study. Setting . Hospital-based clinical research center. Subjects . Healthy adult men and women volunteers. Interventions . Single 400-mg doses of cefixime and ceftibuten, and 500-mg doses of cefuroxime axetil and cefaclor. Measurements and Main Results . Serum concentrations were determined by high-performance liquid chromatography methods. The mean oral clearances of cefixime, cefuroxime axetil, and cefaclor were similar, ranging from 20.4–27.0 L/hour; clearance of ceftibuten was approximately 4-fold less, 5.45 L/hour. The serum half-lives of ceftibuten (2.35 hrs) and cefixime (2.38 hrs) were prolonged compared with those of cefuroxime axetil (1.30 hrs) and cefaclor (0.693 hr). These agents also differed in terms of time to maximum concentration, time to peak plasma level, area under the curve, and apparent volume of distribution, the last reflecting differences in bioavailability. Conclusion . Ceftibuten had a relatively high time to maximum concentration and long half-life, resulting in a 3.5-fold higher area under the curve than cefixime, cefuroxime axetil, and cefaclor. These pharmacokinetic data can be used as a basis to compare the four oral cephalosporins; however, comparative susceptibility data must also be considered.     

Mitoxantrone in refractory acute leukemia in children: A phase I study

Summary Nine children with acute non-lymphocytic leukemia (ANLL), ages 16 months to 16 years (median 7 years), and 15 children with acute lymphocytic leukemia (ALL), ages 10 months to 18 years (median 5 years), were treated with 5-day courses of mitoxantrone (Novantrone®; dihydroxyanthracenedione) as induction therapy. All the children had leukemia which was resistant to conventional therapy and all but one patient had received anthracycline therapy prior to the initiation of this trial. Three patients (two with ANLL, one with ALL) received the drug at a dose of 6 mg/m²/day i.v. for 5 days. Both patients with ANLL achieved partial remissions (PR) (105 and 87 days duration). The child with ALL failed to respond to two courses of the drug, and died of progressive disease 45 days after the institution of therapy. Twenty-one patients (14 with ALL, seven with ANLL) were treated with 8 mg/m²/day i.v. mitoxantrone for 5 days. There were three early deaths (all ALL) which were not felt to be secondary to drug toxicity. Four of the 18 children achieved complete remission (CR) (one ANLL — 35 days; three ALL — 39, 31 and 13 days). One child with ANLL achieved a PR (13 days) and one child with ALL showed improvement in his bone marrow status. Twelve children failed to respond to this therapy.Dose-limiting toxicity was not seen among the patients who received 6 mg/m²/day for 5 days. There were five patients who had mucositis and one patient who had nausea and vomiting among those patients who received 8 mg/m²/day for 5 days. Four of these children had significant decreases in the myocardial shortening fraction as measured by echocardiography. None of these patients had clinical signs of cardiotoxicity.The CR plus PR rate for both dose levels is 33%. Mitoxantrone appears to be an effective agent for remission induction in children with late stage ALL and ANLL. Toxicity was not a significant problem at the doses used in this trial.     

Tolerability of 3-day, once-daily azithromycin suspension versus standard treatments for community-acquired paediatric infectious diseases.

Tolerability of azithromycin oral suspension, 10 mg/kg once daily for 3 days, was assessed in paediatric patients (< or = 18 years) with respiratory or skin and soft-tissue infections. Of 2425 patients evaluated, 1213 received azithromycin and 1212 received standard regimens of amoxycillin/clavulanic acid, cefaclor, cefixime, ceftriaxone, clarithromycin, erythromycin, or penicillin V. The incidence of treatment-related adverse events was significantly lower in patients receiving azithromycin than comparators (7.9 vs. 11.5%, P=0.003), while discontinuation rates were similar (1.0 and 1.1%, respectively). Significantly fewer gastrointestinal events were recorded for azithromycin than comparators (6.5 vs. 9.9%, P=0.002), and their duration was significantly shorter (mean 2.3 vs. 5.0 days, P=0.0001). Azithromycin paediatric oral suspension is well tolerated and associated with significantly fewer adverse events than comparators.     

Short-course therapy with cefaclor for treatment of streptococcal pharyngotonsillitis.

Short-course treatments for streptococcal pharyngotonsillitis with oral cephalosporins or macrolides have resulted in a similar bacteriological and clinical cure rate and better compliance compared with the conventional 10-day course. One hundred and thirty eight of 420 recruited patients had a positive culture for Streptococcus pyogenes and were randomly assigned to receive cefaclor (25 mg/kg/bid) for a 5-day (70 patients) or 10-day (68 patients) course. Patients were assessed clinically and bacteriologically 2-3 days after completing the course and followed up after 20-30 days. All 420 recruited patients belonged to a population of 2800 children who had been previously screened for a streptococcal carrier state to exclude carriers from final evaluation. Clinical cure and bacterial eradication was recorded in 92.8 and 92.6% of patients in groups A and B, respectively. Therefore, short-course therapy with cefaclor may offer an effective alternative treatment to conventional regimens, with potential for better compliance.     

过量奥卡西平致定向力障碍及共济失调

1例6岁男性癫痫患儿,曾先后口服苯妥英钠、拉莫三嗪、丙戊酸钠、苯巴比妥治疗,因不能规律服药致使癫痫反复发作且进行性加重,家属自行给予其口服奥卡西平300 mg、3次/d,上述症状未再发作。但40 d后出现行走不稳、反应迟钝,且癫痫症状也加重。入院诊断为癫痫,全身强直-阵挛发作,奥卡西平致定向力障碍及共济失调。停用奥卡西平,给予丙戊酸钠、还原性谷胱甘肽、维生素C,次日癫痫得到控制。第8天定向力障碍及共济失调消失,癫痫未再发作,遂出院。出院后规律服用丙戊酸钠和氯硝西泮。随访1个月,未再出现癫痫发作、定向力障碍和共济失调。     

Cefaclor concentration in pus from abscess caused by odontogenic infection after a single oral administration

• 1.1. Cefaclor concentrations in serum and pus from abscess of odontogenic infection after a single oral administration of 500-mg cefaclor were assayed and pus concentrations were compared with minimum inhibitory concentration (MIC) of oral streptococci isolated from odontogenic infection.
• 2.2. The mean peak concentrations in serum and pus were found at identical times, 1.5 hr after administration, which were 7.22 and 0.72 μg/ml, respectively.
• 3.3. The mean ratio of pus:serum concentration at the peak time was 0.10.
• 4.4. Most cefaclor concentrations in pus at the peak time (seven of nine cases) exceeded the MIC for 90% of oral streptococci (0.5 μg/ml).

     

Safety and efficacy of lomefloxacin and cefaclor in the treatment of skin and skin structure infections

The purpose of this study was to compare the safety and efficacy of lomefloxacin with that of cefaclor in the treatment of adult secondary bacterial skin and skin structure infections. The study was conducted as a randomized, single-blind comparison. Eighty patients enrolled in the study, of which 74 were evaluable: 37 patients in the lomefloxacin group and 37 in the cefaclor group. Patients received either 400 mg of lomefloxacin orally once daily or 250 mg of cefaclor orally three times daily for 12 days. The most frequent pathogens isolated included Staphylococcus aureus, Streptococcus pyogenes, coagulase-negative staphylococci, and Escherichia coli. The clinical response was similar in both groups (89.1%). The bacteriologic eradication rate was 100% in the lomefloxacin group and 94.5% in the cefaclor group. Adverse events were minimal. Once-daily lomefloxacin is a safe and effective treatment for secondary bacterial skin and skin structure infections caused by susceptible pathogens.     

Phase II evaluation of gallium nitrate by continuous infusion in breast cancer

Summary We evaluated the role of gallium nitrate infusion in the treatment of metastatic breast cancer. Gallium nitrate was administered at 300 mg/m²/day for 7 days every 3 weeks by continuous infusion concomitantly with oral calcium supplement of 500 mg twice daily and oral hydration. Fifteen patients with refractory metastatic breast cancer received such treatment for a total of 30 courses. Median age was 51, and median performance status (Zubrod scale) was 1. These patients had minimal prior chemotherapy (median 1 regimen). All patients were evaluable for toxicity and 14 for response. Nine patients had one to two metastatic sites, five patients had three to four sites. No major objective response was seen, but one patient had a minor response (10 weeks), and another showed no change in disease (16 weeks). Diverse low-grade toxicities were observed, including nausea and vomiting in 11 patients, anorexia in 11, diarrhea in eight, stomatitis in five, dysgeusia in six, musculoskeletal pain in five, skin rash in seven, partially reversible tinnitis and/or mild hearing loss in four and sensory neuropathy in two. A consistent drop in hemoglobin (median of 3.2 g/dL per patient) necessitated blood transfusion in seven patients. There was no granulocytopenia or thrombocytopenia; however, significant lymphopenia was noted. Reversible, moderate nephrotoxicity occurred in two patients. The hypocalcemic effect was consistent, with a median drop in serum calcium of 1.25 mg/dL per course. There was no hepatic toxicity. While no single toxicity was severe, overall toxicity adversely influenced treatment tolerance. Gallium nitrate by continuous infusion, as given in this study, has no activity in metastatic breast cancer.     

Comparative efficacy and safety of 5-day cefaclor and 10-day amoxycillin treatment of group A streptococcal pharyngitis in children

A total of 384 children with group A beta-haemolytic streptococcal (GABHS) pharyngitis were randomized to receive either 40 mg/kg/day of cefaclor in two doses for 5 days (192 patients), or 40 mg/kg/day of amoxycillin in three doses for 10 days (192 patients). The signs and symptoms of pharyngitis were recorded and throat cultures were obtained at presentation and on days 6-7, 11-15, 16-20 and 28-35. Patient compliance was significantly higher in the children treated with cefaclor (100 vs. 95.1%; P = 0.003). At the end of follow-up, the percentage of clinical success was 91.4% for cefaclor and 91.9% for amoxycillin (P = 0.974); bacteriological success was obtained in 85.7 and 89.6% children (P = 0.348), respectively. Both treatments were well-tolerated with adverse event rates of 8.3% in the cefaclor group and 9.4% in the amoxcillin group (P = 0.857). Our study shows that five days' treatment with cefaclor is as effective and safe as the conventional 10-day course of amoxycillin in the treatment of GABHS pharyngitis, but compliance seems to be significantly greater.     

硫酸氢氯吡格雷致过敏反应

1例78岁女性患者因心肌梗死给予阿司匹林100 mg,1次/d口服;硫酸氢氯吡格雷75 mg,1次/d口服。次日晨,患者腹部及双下肢出现瘙痒、红斑。停用硫酸氢氯吡格雷,予氯雷他定10 mg,1次/d口服。1 h后瘙痒缓解、红斑消退。第1天,患者自行服用硫酸氢氯吡格雷75 mg,过敏症状再现,继续服用氯雷他定。4d后,患者行冠状动脉造影﹢经皮冠状动脉介入治疗。术后采用替格瑞洛（90 mg、1次/d口服）联合阿司匹林（100 mg,1次/d口服）抗血小板治疗,随访6个月无不适症状。     

Oral cephalosporins: current perspectives

Oral cephalosporins had been, for years, a small group of compounds belonging to the first or second-generation cephalosporins, with a limited antimicrobial spectrum. New oral first-generation cephalosporins include cefprozil and loracarbef, similar to cefadroxil and cefaclor, respectively, with activity similar to cefaclor but with pharmacokinetic improvements. Second-generation oral cephalosporins are esters of already available cephalosporins, and third-generation oral cephalosporins include a number of drugs whose activity is similar to available parenteral drugs, showing pharmacokinetic advantages and, some of them, better resistance to hydrolysis mediated by extended wide-spectrum β-lactamases. They may be a good alternative against mild to moderate ENT infections, UTIs, STDs, lower respiratory tract and skin and soft tissue infections, mainly in the outpatient setting.     

长期应用卷曲霉素致严重电解质紊乱和横纹肌溶解症

1例53岁女性患者因耐药性肺结核接受乙胺丁醇、吡嗪酰胺、异烟肼和莫西沙星口服联合卷曲霉素肌内注射治疗。治疗11个月后患者出现恶心、呕吐、乏力、四肢无力,逐渐加重,并出现双下肢软瘫。实验室检查示血清钾、钠、钙、磷和镁最低值分别为1.3、128、1.44、0.20和0.38mmol/L,肌酸激酶(CK)13517U/L。患者被诊断为电解质紊乱、横纹肌溶解症。经静脉及口服补充钾、镁、钙和磷及口服螺内酯治疗14 d,患者血钾4.1mmol/L,血钠141mmol/L,血钙2.31mmol/L,血磷1.13mmol/L,血镁0.67mmol/L;四肢肌力恢复良好,可自主行走。     

帕罗西汀致老年患者低钠血症

1例67岁男性脑梗死患者因合并抑郁状态给予帕罗西汀20mg,1次／d口服。5d后患者出现乏力、情感淡漠、食欲减退。实验室检查：血钠128mmol／L（服用帕罗西汀前为136mmol／L）。停用帕罗西汀,改服氟哌噻吨美利曲辛,并给予氯化钠口服。1周后血钠升至134mmol／L,淡漠及乏力感减轻。1个月后复查,血钠142mmol／L。     

健康志愿者头孢克罗尿药浓度测定及3种制剂尿排量比较

目的:比较头孢克罗3种制剂的尿药浓度和尿排量.方法:8名健康志愿者分别单剂量po国产头孢克罗缓释片、头抱克罗普通胶囊和进口头孢克罗缓释片750mg,采用反相高效液相色谱法(RP-HPLC)测定尿中头孢克罗浓度,计算8h分段和累积尿排量及尿排百分率,用配对t检验比较3种制剂尿药浓度和尿排量.结果:国产缓释片与进口缓释片相比,相应各时间段尿药浓度无显著性差异,8h分段和累积尿排量无显著性差异;普通胶囊0～2h尿药浓度和尿排量较缓释片高,2～4、4～6、6～8h均低于缓释片,但3种制剂8h累积尿排量和尿排百分率无显著性差异.结论:缓释片维持有效尿药浓度时间比普通胶囊长.     

Cefaclor concentrations in human serum, gingiva, mandibular bone, and dental follicle following a single oral administration.

1. Cefaclor concentrations in human serum (n = 59), gingiva (n = 46), mandibular bone (n = 39), and dental follicle (n = 42) following a single oral administration of cefaclor (500 mg) were measured by the paper disk method. 2. The peak times of serum, gingiva, mandibular bone, and dental follicle were 1.5, 2, 2, and 1.5 hr, respectively. 3. The mean peak concentrations of serum, gingiva, mandibular bone, and dental follicle were 7.58 micrograms/ml, 3.71, 1.59 and 2.42 micrograms/g, respectively. 4. The concentration ratios of gingiva/serum, mandibular bone/serum, and dental follicle/serum at peak times of the tissues were 0.49, 0.18, and 0.32, respectively. 5. Mean cefaclor concentrations in gingiva, mandibular bone, and dental follicle at peak times exceeded MIC for 90% for clinically isolated strains of alpha-hemolytic Streptococci.     

克洛己新干混悬剂治疗儿童轻度社区获得性肺炎的疗效及安全性

目的探讨克洛己新干混悬剂治疗儿童轻度社区获得性肺炎(community-acquired pneumonia,CAP)的疗效及安全性。方法采用随机数字表法,将南京市中西医结合医院儿科收治的134例轻度CAP患儿分为观察组和对照组,各67例,观察组给予克洛己新干混悬剂治疗,对照组给予头孢克洛治疗,均治疗5 d。比较2组临床疗效、各临床症状改善时间、抗菌效果、服药依从性及不良反应情况。结果观察组总有效率为94.03%,显著高于对照组的76.12%(P<0.05);观察组退热、咳嗽消失、肺啰音消失、血常规恢复正常及X线片改善时间均显著短于对照组(P<0.05);观察组服药依从性优于对照组(P<0.05);2组患儿细菌清除率及不良反应发生率比较,差异均无统计学意义(均P>0.05)。结论克洛己新干混悬剂治疗儿童轻度CAP疗效优于头孢克洛,不良反应较少,且依从性好。