Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections

This multicentre, open-label, randomised trial compared meropenem (0.5 g/8 h) and imipenem/cilastatin (at the commonly used dosage of 0.5 g/6 h) in monotherapy in patients with moderately severe intra-abdominal infections (IAIs). In total, 161 patients were randomised (82 meropenem, 79 imipenem/cilastatin). The mean APACHE II scores in the two groups were 5.8 and 6.4, respectively. At the end of therapy, 65/71 (91.6%) evaluable meropenem recipients were clinically cured or improved, compared to 60/64 (93.8%) imipenem/cilastatin recipients. This difference and that in an intention-to-treat analysis (82.1 vs 86.1%, respectively), were not statistically significant. Both drugs were generally well tolerated. Thus, meropenem 0.5 g/8 h is as clinically effective and well tolerated as imipenem/cilastatin 0.5 g/6 h in moderately severe IAIs.     

蒙特卡洛模拟评价和优化产超广谱β-内酰胺酶大肠埃希菌血流感染抗菌药物给药方案

目的： 评价和优化某院产超广谱β-内酰胺酶大肠埃希菌（ESBLs-EC）血流感染抗菌药物给药方案。方法： 收集该院2019年产ESBLs-EC血流感染对亚胺培南西司他丁、哌拉西林钠他唑巴坦、头孢吡肟、头孢他啶和阿米卡星耐药监测报告,确定亚胺培南西司他丁、哌拉西林钠他唑巴坦、头孢吡肟、头孢他啶和阿米卡星治疗方案,根据各抗菌药物的药动学/药效学（PK/PD）模型,运用蒙特卡洛模拟（MCS）计算5种抗菌药物不同给药方案的达标概率（PTA）和累积反应分数（CFR）,评价疗效和优化出最佳初始给药方案。结果： 亚胺培南西司他丁1 g q12h、1 g q8h和1 g q6h,哌拉西林钠他唑巴坦4.5 g q8h和4.5 g q6h共5种给药方案的CFR ≥ 90%,而头孢吡肟、头孢他啶和阿米卡星所有给药方案CFR均小于90%。结论： 该院产ESBLs-EC血流感染时,经验选择可用亚胺培南西司他丁1 g q12h,哌拉西林钠他唑巴坦4.5 g q8h,不推荐头孢吡肟、头孢他啶和阿米卡星经验性治疗,临床经验性治疗与模拟结果基本一致,个体化治疗则应根据MIC值调整给药方案。     

Cost efficacy of tazobactam/piperacillin versus imipenem/cilastatin in the treatment of intra-abdominal infection

OBJECTIVE: To compare the cost, efficacy and cost efficacy of tazobactam/piperacillin and imipenem/cilastatin in the treatment of intra-abdominal infection. DESIGN: The analysis was retrospective and based on a decision tree. Effectiveness data were obtained from 19 published clinical trials. Direct costs were quantified per patient from the time the decision was made to administer the antibacterial to the end of the first course of treatment or the end of a subsequent course of treatment, if required. The primary end-point was the cost per successfully treated patient. The cost per life saved was also analysed. Various follow-up times were taken into account. PERSPECTIVE: German National Health Insurance funds. STUDY POPULATION: 1744 patients with intra-abdominal infection. INTERVENTIONS: Tazobactam/piperacillin (total daily dosage of 13.5 g/day) and imipenem/cilastatin (total daily dosage of 1.5 to 4 g/day). The mean duration of treatment varied from 5.5 to 8.2 days for tazobactam/piperacillin and 5 to 9.4 days for imipenem/cilastatin. MAIN OUTCOME MEASURE AND RESULTS: Compared with imipenem/cilastatin, treatment with tazobactam/piperacillin was more effective and the overall treatment costs were lower. In the base-case analysis, the cost-efficacy ratio (cost per successfully treated patient) was 7881 German deutschmarks (DM) for tazobactam/piperacillin and DM11,390 for imipenem/cilastatin. The incremental cost-efficacy ratio (per life saved) varied between -DM72,567 and -DM350,738 for tazobactam/piperacillin. Sensitivity analyses revealed that the results were robust against various assumptions on cost parameters, clinical outcomes and length of treatment. All costs reflect 1998 values; $US1 = DM1.85. CONCLUSIONS: This study suggests that compared with imipenem/cilastatin, tazobactam/piperacillin is more cost efficacious in the treatment of intra-abdominal infections and that it offers a cost advantage through fewer relapses and lower daily therapeutic costs.     

Optimising antibiotic dosing regimens based on pharmacodynamic target attainment against Pseudomonas aeruginosa collected in Hungarian hospitals

Owing to increasing resistance rates in Europe, pharmacodynamic analyses were proposed to determine optimal empirical antibiotic therapy against Pseudomonas aeruginosa isolated in Hungary. Minimum inhibitory concentrations for 180 non-duplicate P. aeruginosa collected from 14 hospitals in Hungary were determined by Etest methodology. A 5000-subject Monte Carlo simulation was performed to calculate the bactericidal cumulative fraction of response (CFR) for standard dosing regimens of cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem and piperacillin/tazobactam. In the case of poor CFR, alternative dosage regimens were simulated for selected agents by increasing the infusion time, dose and frequency. Owing to high resistance rates in Hungary, no regimen achieved >90% CFR. CFRs for standard dosing regimens were: meropenem 1g every 8h (q8h), 77.1%; ceftazidime 2g q8h, 75.3%; imipenem 0.5 g every 6h (q6h), 71.7%; and piperacillin/tazobactam 4.5 g and 3.375 g q6h, 72.4% and 71.0%, respectively. Ciprofloxacin achieved significantly lower bactericidal CFRs than any beta-lactam. Prolonged infusion regimens improved the CFR for cefepime, imipenem, meropenem and piperacillin/tazobactam. Overall, the highest CFR (88.1%) was achieved by a 3-h infusion of meropenem 2g q8h. Given the poor CFR predicted with standard dosage regimens against these isolates, it seems prudent to consider alternative dosage strategies such as increasing doses, frequencies or infusion times as well as combination therapy when empirically treating infections caused by P. aeruginosa in Hungary.     

亚胺培南/西司他丁治疗血流感染的蒙特卡洛模拟方案与其临床疗效的相关性研究

目的 根据药动学/药效学(PK/PD)理论,采用蒙特卡洛模拟亚胺培南/西司他丁对大肠埃希菌所致的血流感染给药方案,同时结合亚胺培南/西司他丁对血流感染的临床疗效,对两者进行相关性研究。方法 回顾性调查我院2013年7月-2016年6月引起血流感染的大肠埃希菌对亚胺培南/西司他丁的耐药监测报告,选择亚胺培南/西司他丁给药方案(0.5g q8h、0.5g q6h、1.0g q12h和1.0g q8h),分别计算出蒙特卡洛模拟10000例“真实患者”的累积反应分数(CFR)和临床疗效指数(CEI),用SPSS24.0版软件对CFR与CEI进行相关性分析。结果 亚胺培南/西司他丁给药方案中0.5g q6h的CFR为85.30%;各给药方案的CEI均大于80%。 结论 蒙特卡洛模拟方案CFR和CEI之间呈中等相关(r=0.633),相关性无显著线性关系(P=0.367)。     

Carbapenems versus other beta-lactams in the treatment of hospitalised patients with infection: a mixed treatment comparison

ABSTRACT

Objective: To compare the effectiveness of meropenem with cefepime and piperacillin/tazobactam in the absence of direct comparisons in randomised controlled trials.

Data sources: Two previously conducted systematic reviews, one comparing the carbapenems (ertapenem and imipenem/cilastatin) versus 4th-generation cephalosporins (cefepime) or antipseudomonal penicillins (piperacillin/tazobactam), and the other comparing the carbapenems (imipenem/cilastatin versus meropenem), were updated to provide the basis for this mixed treatment comparison. Searching was completed in April 2007. No restriction was placed on language of publication.

Study selection and data extraction: Randomised controlled trials of adult patients hospitalised with infection and treated with a carbapenem or cefepime or piperacillin/tazobactam. Two reviewers independently assessed the papers against the inclusion/exclusion criteria and for methodological quality with any differences in opinion adjudicated by a third party. Two reviewers independently extracted data on clinical response, bacteriological response, mortality, and adverse events.

Data synthesis: A mixed treatment comparison meta-analysis using Bayesian Markov Chain Monte Carlo simulation was used to perform the indirect comparison. The dataset comprised 34 trials: four comparing ertapenem versus piperacillin/tazobactam, one imipenem/cilastatin versus cefepime, 26 imipenem/cilastatin versus meropenem, three imipenem/cilastatin versus piperacillin/tazobactam. We calculated odds ratios (OR) using imipenem/cilastatin as the common comparator. Meropenem was associated with the highest probability of being the most effective treatment for clinical response (OR?1.52, 95% credible interval [CrI] 1.23–1.87) and bacteriological response (OR?1.45, 95%?CrI?1.15–1.80) with a reduced risk of serious adverse events (overall: OR?0.88, 95%?CrI?0.76–1.02; serious adverse events leading to withdrawal: OR?0.73, 95%?CrI?0.42–1.20; and GI-related: OR?0.76, 95%?CrI?0.55–1.02). There was little difference between the three carbapenems and cefepime on all-cause mortality.

Conclusions: This mixed treatment comparison suggests meropenem has substantial advantages over cefepime, ertapenem, imipenem/cilastatin and piperacillin/tazobactam in the treatment of hospitalised patients with infection.     

应用蒙特卡洛模拟优化哌拉西林他唑巴坦在血液肿瘤化疗后中性粒细胞缺乏伴发热患者中的给药方案

目的：优化哌拉西林他唑巴坦在血液肿瘤化疗后中性粒细胞缺乏伴发热（FN）患者中经验性给药方案。方法：根据哌拉西林他唑巴坦临床药动学和药效学参数,分别以50% f_T>MIC和100% f_T>MIC为目标靶值,用Crystal Ball 11.1.1.3软件对哌拉西林他唑巴坦7种给药方案（3 g q4h、3 g q6h、4 g q6h、4 g q8h,给予0.5 h输注;4 g q6h、4 g q8h,给予3 h输注;16 g持续24 h输注）进行蒙特卡洛模拟,以获得不同治疗方案的达标概率（PTA）,从而优化出最佳的抗感染方案。结果：以50% f_T>MIC为目标靶值,当MIC=16 mg·L^-1时,3 g q4h 0.5 h输注、4 g q6h 3 h输注和16 g 24 h连续输注给药方案的PTA均能达到90%以上;以100% f_T>MIC为目标靶值,当0.5≤MIC≤2 mg·L^-1时,3 g q4h 0.5 h输注、4 g q6h 3 h输注和16 g 24 h连续输注给药方案的PTA均能达到90%以上;当MIC=4 mg·L^-1和MIC=8 mg·L^-1时,仅16 g 24 h连续输注给药方案的PTA能达到90%以上。结论：对于血液肿瘤化疗后FN患者,推荐使用哌拉西林他唑巴坦4 g q6h 3 h输注或16 g 24 h连续输注的给药方案。     

Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms

The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum beta-lactamase (ESBL)-producing organisms. Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N=39) and on pharmacokinetic data from peer-reviewed literature. The desired proportion of the dosing interval that the concentration remains above the MIC (%T>MIC) for the intermittent bolus regimens was >/=40% for piperacillin/tazobactam and >/=60% for cefepime. The desired C(ss)/MIC ratio (where C(ss) is the concentration at steady state) was >/=2 for all continuous infusion (CI) regimens. MIC(50), MIC(90) and %S were, respectively, 64/4mug/mL, 1024/4mug/mL and 33% for piperacillin/tazobactam and 8mug/mL, 16mug/mL and 0% for cefepime. For piperacillin/tazobactam, 3.375g every 4h (q4h) achieved the highest probability of target attainment (43%), followed by 13.5g CI (31%), 3.375g q6h (27%), 4.5g q8h (17%) and 6.75g CI (10%). However, for cefepime, 4g CI had the highest probability of target attainment (77%), followed by 1g q8h (65%), 2g q12h (58%), 3g CI (46%) and 1g q12h (27%). Although the probabilities of target attainment for cefepime were higher than for piperacillin/tazobactam, neither agent achieved a high probability of target attainment and should not be used routinely for the treatment of ESBL infections.     

基于PK/PD模型结合蒙特卡洛模拟评价3种抗菌药物对铜绿假单胞菌感染延长输注给药方案

目的： 应用PK/PD模型结合蒙特卡洛模拟评价3种抗菌药物对铜绿假单胞菌感染的延长输注给药方案。方法： 收集广州市中西医结合医院2020年铜绿假单胞菌对头孢他啶、哌拉西林钠他唑巴坦（8∶1）、美罗培南的药敏报告,制订3种抗菌药物的3 h延长输注及两步法延长输注共12种给药方案,根据各抗菌药物的药动学/药效学（PK/PD）模型参数,应用蒙特卡洛模拟（Monte Carlo simulation,MCS）计算3种抗菌药物不同给药方案对10 000例感染患者的达标概率（probability of target attainment,PTA）及累积反应分数（cumulative fraction of response,CFR）,对各延长输注给药方案进行评价及临床验证。结果： 临床标本共分离出296株铜绿假单胞菌,经MCS模拟3种抗菌药物所有延长输注给药方案的CFR均小于90%,CFR最高的为哌拉西林钠他唑巴坦2.25 g/0.5 h+2.25 g/3 h q6h给药方案（88.10%）;哌拉西林钠他唑巴坦、美罗培南比头孢他啶对MIC中介的铜绿假单胞菌有更高的PTA及CFR,其中美罗培南1 g/0.5 h+1 g/3 h q8h给药方案对MIC=8 μg·mL^-1的耐药铜绿假单胞菌仍有一定的PTA （60.21%）;临床病例验证与MCS结果相仿。结论： 该院铜绿假单胞菌中介/耐药率较高,针对MIC中介以上的铜绿假单胞菌感染,可选择哌拉西林钠他唑巴坦或美罗培南,通过增加给药剂量、频次并使用两步法延长输注给药方式优化抗感染方案。     

Multicenter randomized trial comparing meropenem (1.5 g daily) and imipenem/cilastatin (2 g daily) in the hospital treatment of community-acquired pneumonia

An open, multicenter study with 144 patients, aged between 18 and 94 years, was performed to compare the efficacy and safety of meropenem with imipenem/cilastatin in the hospital treatment of community-acquired pneumonia. Patients were randomized to receive either intravenous meropenem (500 mg every 8 h) or intravenous imipenem/cilastatin (1,000 mg every 12 h). The primary end point was considered to be clinical efficacy and the secondary end points were bacteriological response and safety assessment. At the end of therapy, cure or improvement in signs and symptoms as a satisfactory clinical response was observed in 57 of 64 (89.1%) meropenem-treated patients and in 60 of 66 (90.9%) imipenem/cilastatin patients. The mean duration of treatment was 10 days for meropenem and 9.7 days for imipenem/cilastatin. In patients who were followed up for weeks 2-4, the response was satisfactory (100%) for both treatments. A satisfactory bacteriological response, defined as either presumed or confirmed eradication of all pathogens, was found in eight patients who had received meropenem and in 14 patients who had received imipenem/cilastatin. Response was considered satisfactory in 100% of the meropenem group and in 92.9% of the imipenem/cilastatin group and at follow-up, it was 100% for both treatments. Drug-related adverse events were reported in three (4.2%) meropenem-treated patients and in eight (11.0%) imipenem/cilastatin-treated patients. None of these events was classified as serious. The results of this study show that the clinical and bacteriological efficacy and tolerability of meropenem (500 mg every 8 h) are similar to that of imipenem/cilastatin (1,000 mg every 12 h) in the hospital treatment of community-acquired pneumonia.     

Treatment of diabetic foot infection: an open randomised comparison of imipenem/cilastatin and piperacillin/clindamycin combination therapy

Objective: To compare the clinical outcome and bacteriological response in diabetic patients with a foot infection treated with imipenem/cilastatin or a combination of piperacillin/clindamycin. Methods: Patients hospitalised for diabetic foot lesions Wagner Stages II, III or IV were randomly assigned to receive either imipenem/cilastatin 500 mg QID or piperacillin 3000 mg QID in combination with clindamycin 600 mg TID. Cultures were obtained and clinical observations were made. Results: Forty-six patients (mean age 71.4 +/- 9.8 years) entered the study, 22 received imipenem/cilastatin (IC) and 24 received piperacillin/clindamycin (PCL) combination therapy. In the IC group 22.2% was considered to be clinically cured, 76.2% improved. In the PCL group this was 25.0% and 50.0%, respectively. In the IC treatment group 45.0% of baseline pathogens was eradicated compared to 70.0% in the PCL group. Adverse events were more often reported in PCL treated patients (50.0% vs. 19.0% P < 0.05). Conclusions: Impipenem/cilastatin and piperacillin/clindamycin combination therapy were equally effective in the treatment of patients with diabetic foot lesions. The imipenem/cilastatin regimen caused less side effects.     

哌拉西林／三唑巴坦的临床评价

目的：评价国产哌拉西林／三唑巴坦的疗效和安全性。方法：哌拉西林／三唑巴坦与替卡西林／克拉维酸在下呼吸道腹腔胆道感染中进行随机对照观察,其中治疗组54例,对照组52例;另58例接受哌拉西林／三唑巴坦治疗的下呼吸道、尿路、皮肤软组织感染和败血症例系开放组。治疗下呼吸道、腹腔胆道等感染哌拉西林／三唑巴坦为4．5g q8h静脉滴注,尿路、皮肤软组织感染为4．5g bid静脉滴注,替卡西林／克拉维酸均为每次3．2g q8h静脉滴注。结果：哌拉西林／三唑巴坦治疗下呼吸道感染和腹腔胆道感染的疗效与对照药相仿,但其治疗下呼吸道感染的疗效优于替卡西林／克拉维酸（P＝0．02）,细菌清除率两组相仿,两组中均无不良反应者。哌拉西林／三唑巴坦（包括治疗组和开放组）治疗上述感染的总有效率为92．0％（103／112）,细菌清除率97．3％（103／111）,不良反应发生率为1．8％（2／112）,分别为腹泻及ALT升高各1例。结论：国产哌拉西林／三唑巴坦治疗常见性细菌感染疗效确切,不良反应少而轻微,其疗效较替卡西林／克拉维酸相似或略优,安全性与替卡西林／克拉维酸相仿。     

头孢哌酮/舒巴坦与亚胺培南/西司他丁治疗重症医院获得性肺炎的比较

目的:比较头孢哌酮/舒巴坦(舒普深)与亚胺培南/西司他丁(泰能)对重症医院获得性肺炎(HAP)的疗效。方法:回顾性分析60例重症医院获得性肺炎(男42例,女18例,年龄42～89 a),其中30例用头孢哌酮/舒巴坦3.0 g加入0.9％生理盐水250mL静滴,q12h;30例用亚胺培南/西司他丁0.5g加入0.9％生理盐水250mL静滴,q 6 h,均7～10 d为一疗程。结果:头孢哌酮/舒巴坦组临床有效率70.0％,痊愈率60.0％;亚胺培南/西司他丁组临床有效率76.7％,痊愈率63.3％,两组间相差无统计学意义(P>0.05)。结论:头孢哌酮/舒巴坦与亚胺培南/西司他丁治疗重症医院获得性肺炎疗效相近。     

1例断腕再植患者的药学监护

1例33岁女性患者,因车祸致右腕离断入院.入院行断腕再植术,3d后,患者出现创伤后肝损伤,ALT 48 IU-L-1,AST165 IU-L-1,选用保肝药物还原型谷胱甘肽进行治疗,10d后转氨酶恢复正常.患者伤口出现感染,根据细菌培养及药敏分析结果,针对铜绿假单胞菌选择哌拉西林/他唑巴坦4.5g,q8h,ivgtt进行治疗,用药12d后,患者出现白细胞减少,立即停药.新的细菌培养结果为铜绿假单胞菌和鲍曼不动杆菌混合感染,根据药敏分析结果,选择亚胺培南/西司他丁1g,q12h,ivgtt 治疗.一周后,分泌物培养结果为鲍曼不动杆菌,显示治疗有效,继续亚胺培南/西司他丁抗感染治疗,10d后感染治愈,患者出院.     

Piperacillin/tazobactam: a pharmacoeconomic review of its use in moderate to severe bacterial infections.

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well-tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/ clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modelled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. CONCLUSIONS: Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.     

PK/PD模型结合蒙特卡洛模拟评价和优化耐碳青霉烯类铜绿假单胞菌抗菌药物给药方案

目的： 评价和优化耐碳青霉烯类铜绿假单胞菌感染抗菌药物给药方案。方法： 收集中山市人民医院2019年耐碳青霉烯类铜绿假单胞菌对头孢他啶、头孢吡肟、哌拉西林钠他唑巴坦和阿米卡星耐药监测报告,确定头孢他啶、头孢吡肟、哌拉西林钠他唑巴坦和阿米卡星治疗方案,根据各抗菌药物的PK/PD模型,运用蒙特卡洛模拟计算4种抗菌药物不同给药方案的达标概率（PTA）和累积反应分数（CFR）,评价疗效和优化出最佳初始给药方案。结果： 4种抗菌药物15种给药方案CFR均<90%。当最低抑菌浓度（MIC）≤ 2 μg·mL^-1时,4种抗菌药物常规剂量下的给药方案均能达到满意的治疗效果,当MIC ≤ 16 μg·mL^-1时,可目标性选择头孢他啶2 g（q8h）、头孢吡肟2 g（q8h）和哌拉西林钠他唑巴坦4.5 g（q8h）给药方案治疗,当MIC=32 μg·mL^-1时,只有哌拉西林钠他唑巴坦4.5 g（q6h）给药方案PTA>90%,当MIC>32 μg·mL^-1时,所有给药方案PTA均<90%。4种抗菌药物MIC值的敏感相关性为范围-88.9%~-96.7%。结论： 在CRPA感染经验性治疗时,单药治疗并不能达到满意的抗感染治疗效果,应考虑联合用药,可选用较高剂量和增加给药频次的抗假单胞菌β内酰胺类抗菌药联合阿米卡星。MIC值是影响4种抗菌药物治疗效果的最主要因素,临床上应重视细菌耐药的培养,可根据MIC值调整给药方案进行目标治疗。     

临床药师参与1例颈深间隙感染并脓毒性休克抗感染治疗分析

目的:探讨临床药师在颈深间隙感染并脓毒性休克患儿治疗中发挥的药学指导作用.方法:临床药师参与1例颈深间隙感染并脓毒性休克患儿的会诊.根据患儿病情特点、病原学及药敏结果,结合抗菌药物的杀菌活性、PK/PD特点以及组织分布等,将用药方案"万古霉素、亚胺培南/西司他丁、甲硝唑氯化钠注射液及注射用头孢曲松钠"调整为"青霉素G每...     

Imipenem/cilastatin versus piperacillin/tazobactam plus amikacin for empirical therapy in febrile neutropenic patients: results of the COSTINE study

BACKGROUND: Combinations of beta-lactams plus aminoglycosides have become standard therapy for suspected infections in patients with profound neutropenia. However, it is not clear whether such combinations are advantageous over therapy with a broad-spectrum antibiotic. OBJECTIVE: To assess the clinical effectiveness and the cost-effectiveness ratio of empirical therapy of febrile neutropenia with imipenem/cilastatin (I/C) versus piperacillin/tazobactam plus amikacin (P/T+A). RESEARCH DESIGN AND METHODS: Prospective, multicenter observational study with 2 matched parallel cohorts treated with I/C (500 mg/6 h iv) or P/T+A (P/T: 4 g/6 h iv; A: 20 mg/kg/day iv). MAIN OUTCOME MEASURES: Therapeutic success was defined as the resolution of fever following > or = 7 days of unchanged antibiotic treatment. An economic comparison was conducted focusing on the daily treatment costs, and the management of its toxicity. RESULTS: There were 343 eligible patients (180 I/C, 163 P/T+A), of whom 290 were evaluable for the primary clinical effectiveness analysis. Follow-up information beyond 7 days of study inclusion was only available for 52% of all evaluable patients. Treatment success was observed in 42% of I/C patients compared with 31% of P/T+A patients (95% CI: -0.01, 21.4). The incidence of drug-related adverse experiences was 13% for I/C and 6% for P/T+A, with no differences in moderate or severe adverse experiences nor in those causing discontinuation of antibiotic therapy. Treatment costs were 189.55 euros (95% CI: 127.46-251.46) lower per episode of febrile neutropenia for patients treated with I/C. CONCLUSIONS: The clinical effectiveness of I/C was similar to that of P/T+A. In both treatment groups toxicity was low and did not limit antibiotic therapy. Resource consumption was lower with I/C.     

亚胺培南治疗老年重症下呼吸道感染56例临床分析

目的评价亚胺培南/西司他丁钠盐治疗老年重症下呼吸道感染的疗效、细菌耐药及安全性。方法采用回顾性研究,用亚胺培南/西司他丁钠盐治疗呼吸重症监护室(RICU)老年重症下呼吸道感染56例,观察疗效、细菌耐药及安全性。结果用药后临床有效率、临床痊愈率、细菌阴转率和细菌清除率依次为91.2％、82.4％、76％、73.8％;102株细菌高敏率、敏感率和耐药率分别为72.4％、79.4％、20.6％,出现不良反应13例,其中4例腹泻、6例并发真菌感染,1例肠道难辩梭状芽孢杆菌感染,未发现其它副作用。结论亚胺培南/西司他丁钠盐是一个安全、有效的治疗老年重症下呼吸道感染的抗菌药物,但因耐药菌株也在不断增加,因此应密切监测致病菌耐药性的产生和变化,及时调整治疗方案。     

关于亚胺培南西司他丁钠致一儿童牙齿黄染的讨论

8岁男童因患肺部感染，静脉输注亚胺培南西司他丁钠（1g，每日2次）抗感染治疗，用药4天后发现牙齿黄染，用药10天黄染进一步加深，停药后1月牙齿着色未变化。其牙齿黄染虽经刷牙未能改变，而最终通过牙科医生洗牙得以去除。