奈替米星与阿米卡星临床疗效观察

目的以阿米卡星为对照评价奈替米星治疗下呼吸道感染的临床有效性及安全性。方法共人选病例132例，可评价疗效者102例，其中试验组（奈替米星）与对照组（阿米卡星）分别为52例与50例。安全性评价人选病例113例，两组分别为56例与57例。给药方法试验组每次200mg，每日1次，对照组每次200mg，每日2次，两组疗程均为7～14天。结果试验组与对照组的临床有效率分别为84．61％与64．00％，细菌清除率分别为90．91％与66．67％，敏感菌百分率分别为93．18％与71．43％，听力下降发生率分别为1．79％与15．79％。以上结果经统计学处理两组差异有显著性。结论奈替米星为治疗下呼吸道感染的安全、有效的抗菌药物。     

头孢他啶联合奈替米星或左氧氟沙星治疗老年医院获得性肺炎的对照观察

目的 观察头孢他啶联合奈替米星治疗老年医院获得性肺炎（Hospital acquired pneumonia）的疗效。方法 将42例病人随机分为两组，治疗组22例，予头孢他啶2．0g静滴，每日2次；同时予奈替米星0．2～0．3g静滴，每日11次。对照组20例予头孢他啶2．0g静滴，每日2次；同时予左氧氟沙星0．5g静滴，每日1次。疗程均为7-14d。结果 治疗组与对照纽的有效率分别为81．8％和80％；两组的细菌清除率分别为84．6％和83．3％；药物不良反应发生率分别为13、6％和10％，两组比较均无统计学意义（P〉0．05）。结论 头孢他啶联合奈替米星治疗老年医院获得性肺炎安全、有效。     

莫西沙星和奈替米星联合方案治疗耐多药肺结核的近期疗效观察

目的评价含莫西沙星和奈替米星联合化疗方案对耐多药肺结核(MDR-PTB)的疗效。方法将56例MDR-PTB患者随机分为两组,治疗组28例采用以莫西沙星(M)和奈替米星(N)为主,联合力克肺疾(D)、丙硫异烟胺(Pt)、吡嗪酰胺(Z);对照组28例采用以左氧氟沙星(V)和阿米卡星(A)为主,联合D、Pt、Z;疗程均为21个月。结果:治疗组痰菌阴转率92.9%,对照组痰菌阴转率67.9%,治疗组明显高于对照组(P<0.05)。结论含莫西沙星和奈替米星方案治疗耐多药肺结核有助于痰菌阴转和病灶吸收,药物不良反应低,值得在临床推广应用。     

奈替米星治疗肺结核的临床观察

为了探索新一代氨基糖甙类抗生素奈替米星（NTI）对肺结核的疗效、安全性及毒副作用，我们作了临床观察，报告如下。     

呼吸道铜绿假单胞菌对氨基糖苷类抗生素药敏试验结果及耐药规律

目的了解呼吸道铜绿假单胞菌对氨基糖苷类抗生素敏感情况及耐药规律。方法收集并分析361株呼吸道铜绿假单胞菌对氨基糖苷类抗生素药敏资料,并探讨其耐药规律。结果本院呼吸道铜绿假单胞菌对阿米卡星最敏感,敏感率达82.2％。其次为奈替米星,敏感率46.3％。庆大霉素和妥布霉素的耐药率约60％。对4种抗生素同时敏感菌株为115株,占总数的31.9％,同时耐药菌株49株,占13.6％。对阿米卡星敏感而对其它3种抗生素耐药菌株79株,占21.9％。对阿米卡星和奈替米星敏感,而对另两种抗生素耐药菌株为41株,占11.4％。结论阿米卡星在氨基糖苷类抗生素中对铜绿假单胞菌最敏感。铜绿假单胞菌对4种抗生素存在不同程度交叉耐药,妥布霉素与庆大霉素交叉耐药更严重。     

奈替米星和司帕沙星联合治疗耐多药肺结核近期疗效分析

目的评价含奈替米星和司帕沙星联合对耐多药肺结核（MDR-PTB）的疗效。方法 348例MDR-PTB患者,随机分为两组,以氧氟沙星和丁胺卡那霉素作为对照组。治疗组174例采用3NSDTZ（E）/9SDTZ（E）方案治疗,对照组174例采用3AODTZ（E）/9ODTZ（E）方案治疗。结果第3个月末,治疗组痰菌转阴率为72%,明显优于对照组（48%）,两组对照有统计学上的显著性意义（P〈0.05）。疗程结束时,治疗组痰菌转阴率为89%,明显优于对照组（68%）,两组对照有统计学的显著性意义（P〈0.05）。结论以奈替米星和司帕沙星联合治疗MDR-PTB疗效肯定,痰菌转阴速度快,值得继续临床探索。     

雾化吸入阿米卡星在气管支气管结核患者体内的药物分布特点

目的讨论气管支气管结核(EBTB)患者接受雾化吸入或静滴阿米卡星治疗后,气道分泌物及血浆中阿米卡星的分布特点。方法 20例患者分为两组(每组10例),分别接受雾化吸入阿米卡星200mg和静滴阿米卡星200mg,1次/d;5天后,患者分别在治疗结束后0、2、6、8、12、24 h检测气道分泌物和血浆中阿米卡星的浓度。结果雾化吸入组气道分泌物中的药物浓度峰值中位数为0.3836μg·m L~(-1)(0.1725-0.5269μg·m L~(-1)),血浆中药物浓度峰值中位数为22.87μg·m L~(-1)(15.53-30.12μg·m L~(-1));静脉给药组气道分泌物药物浓度峰值中位数为0.3836μg·mg~(-1)(0.1725-0.5269μg·mg~(-1)),血浆中药物浓度峰值为22.87μg·m L~(-1)(15.53-30.12μg·m L~(-1))。结论与静滴相比雾化吸入阿米卡星气道分泌物中的药物浓度远高于常见的MIC,而血浆中药物浓度却远低于其毒性浓度,雾化吸入阿米卡星治疗EBTB可能为一种安全有效的治疗方法。     

粪肠球菌感染抗菌药物联合应用的体外效应研究

目的　评价万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星和加替沙星 6种抗菌药物分别与第一代头孢菌素头孢硫脒联合用药 ,对于临床分离的粪肠球菌 (Enterococcusfaecalis,Ef)的体外联合抗菌效应。方法　采用棋盘法设计 ,微量肉汤稀释法测定。测定不同浓度组合的 6组抗菌药物对 30株临床分离的革兰阳性球菌的最低抑菌浓度 ,并计算FIC指数。FIC≤ 0 .5为协同作用 ,0 .5 2为拮抗作用。结果　头孢硫脒对粪肠球菌的MIC50 为 2～ 8mg L ,与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星、加替沙星联合应用后 ,其MIC50 分别显著地降低至 0 .1 2 5 ,0 .2 5 ,0 .2 5 ,0 .2 5 ,0 .2 5 ,0 .2 5mg L。FIC指数分布 :FIC≤ 0 .5占 50 %～ 86 .7% ;0 .5 2为 0。结论　 6种抗菌药物与头孢硫脒分别联合用药后 ,对粪肠球菌基本表现为协同作用和相加作用 ,并以协同作用为主 ,无关作用较少 ,无拮抗作用     

硫酸依替米星的临床应用研究进展

合理使用抗生素是治疗细菌感染的关键。氨基糖苷类抗生素对需氧革兰阴性杆菌和革兰阳性球菌均有强大的杀灭作用,与青霉素类或头孢菌素类合用可取得协同效果,并具有较好的抗菌后续效应,但其耳毒性和肾毒性等不良反应使其临床应用处于停滞状态。80年代末,随着奈替米星等新一代抗菌活性强、不良反应较少的氨基糖苷类抗生素出现,氨基糖苷类抗生素再次成为临床一线用药。我国自主研发的新一代氨基糖苷类抗生素硫酸依替米星为半合成水溶性氨基糖苷类广谱抗生素,     

替米沙坦治疗轻中度高血压的临床疗效和安全性--多中心随机对照临床试验

目的：（1）比较替米沙坦40mg或80mg与氯沙坦50mg或100mg每天一次口服治疗轻中度高血压的疗效和安全性；（2）评价替米沙坦40mg每天一次口服治疗轻中度高血压的24h降压效果及谷／峰比值。方法：（1）多中心、随机、双盲、双模拟平行分组试验。330例轻中度高血压（95mm Hg≤舒张压＜110mm Hg，收缩压＜180mm Hg,1mm Hg=0.133kPa)患被随机分入替米沙坦组（164例）和氯沙坦组（166例），分别每天一次口服替米沙坦40mg或氯沙坦50mg。4周后如坐位舒张压≥90mm Hg，则改为替米沙坦80mg或氯沙坦100mg每天一次口服。（2）开放试验。同样条件的20例患服用替米沙坦40mg共6周，于替米沙坦治疗前后各进行24h动态血压监测。结果：（1）治疗8周末，替米沙坦组的坐位收缩压及舒张压下降幅度大于氯沙坦组（12．5mm Hg vs 9.4mm Hg,P=0.037及10.9mm Hg vs 9.3mm Hg,P=0.030);(2)替米沙坦降低轻中度高血压的总有效率高于氯沙坦（70．1％ vs 58.7%,P=0.020);(3)替米沙坦级瑟氯沙坦组的不良事件发生率相似（23．2％ vs 22.9%,P=0.952);(4)替米沙坦40mg每天一次口服，其收缩压的谷／峰比值为66．5％，舒张压的谷／峰比值为76．8％；24h平均血压下降10．2／7．8mm Hg，用药末6h的平均血压下降10.0/9.2mm Hg。结论：（1）替米沙坦40mg或80mg每天一次口服治疗轻中度高血压安全有效；（2）替米沙坦适合每天一次服用，其降压作用可维持24h。     

Bactericidal activity of antibiotics alone and in combination against Enterococcus faecalis in a pharmacodynamic model.

We evaluated the bactericidal kinetics of teicoplanin, mezlocillin, netilmicin, and ciprofloxacin alone and in dual combinations against strains of Enterococcus faecalis susceptible or resistant to ampicillin in a pharmacodynamic model reproducing in bacterial culture in active human plasma or Mueller-Hinton broth the serum kinetics of these antibiotics in humans. Killing was not different in cultures grown in plasma and those grown in broth. Antibiotics used alone had no or low bactericidal activity except for high-dose ciprofloxacin (600 mg intravenously [iv] twice daily or 750 mg orally twice daily), which achieved a 3- to 4-log reduction in colony-forming units (cfu). Netilmicin was equally active at 6 mg/kg once a day or 2 mg/kg three times daily in all combinations. No major increase in bactericidal activity was detected in any combination that included mezlocillin. Maximal synergistic killing was observed for the combination of teicoplanin plus netilmicin (both at three-times daily and once-daily dosing), which sterilized the bacterial cultures (initial inoculum, 10(6) cfu/mL). Combinations of ciprofloxacin at 600 mg iv twice daily and 750 mg orally twice daily plus either teicoplanin or netilmicin were less synergistic but equally effective in total killing as a result of the high bactericidal activity of ciprofloxacin alone.     

Inactivation of netilmicin by carbenicillin

Summary Netilmicin was added to human serum and stored at various temperatures and carbenicillin concentrations prior to bioassay. Inactivation of netilmicin increased with temperature and carbenicillin concentration. The order of inactivation of aminoglycosides was: tobramycin > gentamicin, netilmicin > amikacin.

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Inaktivierung von Netilmicin durch Carbenicillin

Zusammenfassung Netilmicin wurde Humanserum zugesetzt und vor der biologischen Auswertung bei verschiedenen Temperaturen und Carbenicillinkonzentrationen gelagert. Die Inaktivierung von Netilmicin nahm mit steigender Temperatur und Carbenicillinkonzentration zu. Die Inaktivierung von Aminoglykosiden ergab die Reihenfolge: Tobramycin > Gentamycin > Netilmicin > Amikacin.

     

Clinical evaluation of netilmicin therapy in serious infections.

Netilmicin, a new semisynthetic aminoglycoside, was evaluated in the therapy of 33 episodes of infection in 30 patients. Eighteen patients had documented bacteremia. Infection sites included pulmonary, urinary tract and soft tissue areas. A complete bacteriologic and clinical cure rate of 85 per cent was achieved. No treatment failures occurred in the bacteremic group. Although netilmicin is less effective than gentamicin in vitro against Pseudomonas, it was clinically and bacteriologically effective. Netilmicin bacteriologic cures occurred in patients whose organisms were inhibited by 6.2 microgram/ml or less of netilmicin. Despite a uniform dosing protocol, a wide range of netilmicin serum levels was obtained. Adverse effects were limited to one case of transient nephrotoxicity and one Candida urinary suprainfection. Netilmicin appears to be an effective, safe agent for the therapy of serious infections.     

Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone

PURPOSE: Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside. PATIENTS AND METHODS: We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin. RESULTS: Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses. CONCLUSION: Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment.     

Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments

The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/l. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacterial agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T1/2) of pefloxacin was longer than that of ofloxacin, but the T1/2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1%, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose--600 mg daily--such a dosage may be only moderately effective against human tuberculosis.     

Serum magnesium concentration in children with functional constipation treated with magnesium oxide

AIM:To determine whether hypermagnesemia recently reported in adult patients possibly develops in children with functional constipation taking daily magnesium oxide.METHODS:We enrolled 120 patients (57 male and 63 female) aged 1-14 years old (median:4.7 years) with functional constipation from 13 hospitals and two private clinics.All patients fulfilled the Rome Ⅲ criteria for functional constipation and were treated with daily oral magnesium oxide for at least 1 mo.The median treatment dose was 600 (500-800...     

Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia

The pharmacokinetics of busulfan, given as a single daily dose (either 4 mg/kg or 150 mg/m2), was determined in 22 children undergoing bone marrow transplantation for acute leukemia. The single daily dose regimen showed similar pharmacokinetics to previously reported regimens of 4 x 1 mg/kg, except for fourfold higher mean peak plasma levels and negligible trough levels. Daily systemic exposure for single dose regimens based on weight (4 mg/kg) or surface area (150 mg/m2), respectively were very similar to regimens of (4 x 1 mg/kg) or (4 x 37.5 mg/m2). Dose (milligrams per kilogram), peak plasma level, and area under the curve (AUC) were all higher in 12 children treated with 150 mg/m2 busulfan than in 9 children treated with 4 mg/kg. AUC was age dependent for the 4 mg/kg dose but not for the 150 mg/m2 dose. The use of a 150 mg/m2 dose allows escalation of the dose above 4 mg/kg, eliminating the tendency for younger children to receive lower systemic exposure. Little toxicity was observed in this study. Clearance and distribution volume correlated negatively with age, and AUC correlated positively with dose (milligram per kilogram). Administration of busulfan as crushed rather than whole tablets reduced the delay time for appearance of busulfan in plasma but had no effect on absorption or other pharmacokinetic parameters.     

Enzyme induction observed in healthy volunteers after repeated administration of rifapentine and its lack of effect on steady-state rifapentine pharmacokinetics: part I.

OBJECTIVE: To determine the effects of rifapentine on hepatic mixed function oxidase activity and to assess the effect of enzyme induction on the steady-state pharmacokinetics of rifapentine. STUDY DESIGN: Twenty-three healthy males were randomized to receive two of the following treatments in a two-period, four-treatment, incomplete block, crossover design: single daily oral rifapentine doses of 150 mg (group A), 300 mg (group B), or 600 mg (group C) on study days 1 and 4-10, or single oral rifapentine 600 mg doses given every 3 days for a total of four doses (group D). Serial blood samples were collected after the first and last rifapentine dose and assayed for rifapentine and its active metabolite, 25-desacetyl-rifapentine. Urine was collected for determination of cortisol and 6-hydroxycortisol concentrations. RESULTS: The ratio of 6beta-hydroxycortisol:cortisol increased during rifapentine administration (+229%, +317%, and +357% on day 10 for groups A, B, and C, respectively). Ratios returned to baseline 2 weeks after the last dose. The per cent increase in the ratio of 6beta-hydroxycortisol:cortisol following daily doses (+357%) was much higher compared with every 72-hour dosing (+236%). Single-dose and steady-state comparisons of AUCss(0-24) and AUC(0-->infinity) for both rifapentine and 25-desacetyl-rifapentine were similar (P = NS) at corresponding doses of rifapentine. Mean t(1/2) at steady-state was 84-98% of corresponding single-dose values. CONCLUSION: Rifapentine is a potent inducer of CYP3A activity. However, single-dose pharmacokinetics of rifapentine predict steady-state exposure, indicating no autoinduction of rifapentine metabolism with repeated administration. Enzyme activity returns to predose levels within 2 weeks of the last daily dose of rifapentine.     

Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism

OBJECTIVE: Previous studies of the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a favourable result with methimazole (MMI). However, the efficacy of a single daily dose of propylthiouracil (PTU) was inconsistent. The present prospective randomized study was conducted to compare the efficacy of a single daily dose of MMI and PTU in the induction of euthyroidism in patients with Graves' disease. SUBJECTS: Seventy-one patients with newly diagnosed Graves' disease were studied. METHODS AND MEASUREMENTS: Patients were randomized to two groups to receive once daily dose of either 15 mg MMI or 150 mg PTU for 12 weeks. The therapeutic efficacy was determined biochemically by serum total T3, total T4 and TSH levels at baseline and at 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline characteristics. Serum total T3 levels of the MMI group were significantly lower than those of the PTU group after four weeks of the treatment (3.54 +/- 0.72 vs. 5.49 +/- 2.74 nmol/l, P < 0.05) through the end of the study (2.22 +/- 1.42 vs. 4.30 +/- 1.78 nmol/l, P < 0.05). The changes in serum total T4 levels occurred in the same direction as serum total T3 levels but a significant difference was observed only after eight weeks of the treatment (MMI vs. PTU; 101.67 +/- 54.05 vs. 176.32 +/- 66.92 nmol/l, P < 0.05). At the end of the study, more patients in the MMI group had both serum total T3 and T4 levels less than the upper limit of the normal range compared to the PTU group (77.1% vs. 19.4%). Hypothyroidism was observed in 31.4% of the patients in the MMI group but not in the PTU group. CONCLUSIONS: During 12-weeks' treatment of Graves' hyperthyroidism, a single daily dose of 15 mg of MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg of PTU. Once daily regimen of MMI not only decreased serum T3 and T4 levels more rapidly but also induced euthyroidism four times more effectively than did the once daily regimen of PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of hyperthyroidism.     

Single-dose treatment with netilmicin for different clinical forms of urinary tract infections

Summary A group of 44 patients with various clinical forms of urinary tract infections received a single dose of 300 mg netilmicin i.m. The treatment was efficacious in all patients with infections which were negative in the antibody-coated bacteria test and not complicated by anatomic and/or functional abnormalities of the kidneys and urinary tract. After three weeks the recurrence rate was only 19%. Single-dose treatment also proved very effective against urinary tract infections in renal transplant patients whose infection is almost always located in the lower urinary tract. In contrast, the short-term results of treatment were much poorer in complicated infections and particularly in urinary tract infections which were positive in the antibody-coated bacteria test; here, the recurrence rate was 67%.

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Therapie verschiedener klinischer Formen von Harnwegsinfektionen mit einer Einzeldosis von Netilmicin

Zusammenfassung 44 Patienten mit verschiedenen klinischen Formen von Harnwegsinfektionen wurden mit einer Einzeldosis von 300 mg Netilmicin i.m. behandelt. Die Therapie erwies sich als sehr wirksam gegen Infektionen bei allen Patienten mit negativen Ergebnissen im Test auf antikörperbeladene Bakterien und ohne anatomische und/oder funktionelle Nieren- und Harnwegsanomalien. Nach drei Wochen rezidivierte die Infektion nur bei 19% der Patienten. Nierentrans-plantierte patienten, bei denen die Infektion fast immer in den unteren Harnwegen lokalisiert ist, sprachen ebenfalls sehr gut auf die Behandlung mit einer Einmaldosis Netilmicin an. Die kurzfristigen Behandlungsergebnisse waren dagegen bei komplizierten Infektionen, insbesondere bei Harnwegsinfektionen mit positivem Test auf antikörperbeladene Bakterien, sehr viel schlechter; die Rezidivrate betrug 67%.