Limiting cefotaxime pediatric dosing to adult standards: a pharmacokinetic simulation study.

OBJECTIVE: The recommended cefotaxime dose of 50 mg/kg every six to eight hours for pediatric patients with a body weight greater than 20 kg exceeds the standard 1-gram dose recommended for adult patients. This study estimated whether limiting the cefotaxime dose recommended for children with mild to moderate infections to a standard 1-gram dose would achieve serum concentrations and time above the MIC90 comparable to those in adults. METHODS: Serum concentration profiles were simulated from mean cefotaxime pharmacokinetic parameters that have been published for children and for adults using widely available spreadsheet software. The simulations employed an open, one-compartment, multiple-dose model and were calculated using a common commercial spreadsheet. The model was used to predict serum concentrations using dosage regimens of 1 g or 50 mg/kg administered every six or eight hours in pediatric patients of various weights with pediatric pharmacokinetic parameters and 1 g every six or eight hours for adult patients with adult pharmacokinetic parameters. The time that cefotaxime concentrations exceeded the MIC90 for pediatric pathogens was also calculated. RESULTS: The 50 mg/kg pediatric dosing regimens administered every 8 hours (q8h) or every 6 hours (q6h) consistently produced peak serum concentrations and area under the concentration versus time curve (AUC) values higher than those in adults. Serum concentrations and AUCs generated for the 1-gram regimens for various pediatric weight categories were also above those predicted in adults. The time above the MIC90 for pediatric patients was equivalent to or exceeded those of the adult simulations for all pathogens. CONCLUSIONS: The results support the concept of limiting cefotaxime dosage regimens to 1 g administered every 6 or 8 hours for mild to moderate infections in children weighing more than 20 kg. This dosage regimen could lead to dose standardization procedures, which could produce reductions in drug costs associated with individualized dosage preparation.     

1例产超广谱β-内酰胺酶肺炎克雷伯菌肺炎患儿的抗感染治疗分析

目的:探讨产超广谱 茁鄄内酰胺酶(ESBLs)肺炎克雷伯菌肺炎患儿抗感染治疗方案。 方法:临床药师对 1 例产 ESBLs 肺炎克雷伯菌肺炎患儿抗感染治疗方案进行分析,寻找疗效不佳的可能原因,优化抗感染治疗方案。 结果:医疗机构相关性肺炎(HCAP)患儿经验性抗感染治疗选择头孢哌酮/舒巴坦(68 mg/ kg,q 12 h)合理,但给药第 5 天起降低头孢哌酮/ 舒巴坦剂量(45mg/ kg,q 12 h)可能是导致疗效不佳的主要原因;肺泡灌洗液提示产 ESBLs 肺炎克雷伯菌感染,临床药师建议更换抗生素为亚胺培南/西司他丁(15 mg/ kg,q 6 h),患儿感染得到有效控制,治愈出院。 结论:产 ESBLs 肺炎克雷伯菌感染患儿病情评估为轻中度,可以选择含酶抑制剂的复方制剂,对于有基础疾病的患儿,头孢哌酮/ 舒巴坦建议选择足量足频次(如 50 mg/kg,q 8 h)的给药方案;如患儿病情评估为重度,建议选择碳青霉烯类抗生素,选择碳青霉烯类药物时要考虑不同药物之间疗效和不良反应的差异。     

Evaluation of an empirical dosing schedule for gentamicin in neonates

The standard gentamicin dosing recommendations for neonates appear to be inappropriate because they fail to consider the influence of neonatal development on gentamicin pharmacokinetics. Recent reports have emphasized that the standard regimens of 2.5 mg/kg q8-12h produce steady-state trough serum concentrations greater than 2 micrograms/ml in up to 91 percent of preterm infants of less than 35 weeks' gestation. A new dosing schedule based on postconceptional age (PCA) was developed to provide a better guideline for initiating and maintaining gentamicin therapy in neonates: PCA greater than 34 weeks, 2.5 mg/kg iv q12h; PCA 28-34 weeks, 2.5 mg/kg iv q16h; PCA less than 28 weeks, 2.5 mg/kg iv q24h. The new dosing schedule reduced the number of neonates with elevated trough concentrations (greater than 2 micrograms/ml) from 68.4 percent to 33-40 percent. Pharmacokinetic parameters for gentamicin in the various PCA groups were determined. Volume of distribution was constant across age groups (0.5 +/- 0.09 L/kg). Elimination rate constants (kel), half-lives, and clearance rates (Cl) ranged from 0.069 +/- 0.02 to 0.14 +/- 0.04 h-1, 10.71 +/- 2.92 to 6.04 +/- 1.24 h, and 0.58 +/- 0.25 to 0.93 +/- 0.24 ml/kg/min, respectively. Significant relationships were found between kel and Cl and patient age and weight; significant correlations were found between actual and estimated (based on PCA and weight) kel and Cl. Variability in kel and Cl estimated was considerable in spite of the correlations. The observed variability stresses again the need for pharmacokinetic monitoring of gentamicin therapy in neonates.     

某院鲍曼不动杆菌血流感染治疗方案的制定

目的：制定某院鲍曼不动杆菌血流感染的治疗方案。方法：收集某院2015-2016年血标本培养出的鲍曼不动杆菌39株,测定对氨苄西林舒巴坦,替加环素,亚胺培南,美罗培南的最低抑菌浓度。运用蒙特卡洛方法计算不同方案的达标概率（PTA）和累积反应分数（CFR）。结果：氨苄西林舒巴坦3 g q6h对鲍曼不动杆菌的CFR为66.05%,替加环素50 mg q12h,100 mg q12h的CFR分别为95.75%和99.77%,亚胺培南1 g q8h,q6h和美罗培南1 g q8h,q6h的CFR分别是67.74%,96.56%和74.19%,88.8%。结论：某院鲍曼不动杆菌血流感染时,经验选择可用替加环素50 mg q12h,100 mg q12h和亚胺培南1 g q6h方案。目标治疗应根据最低抑菌浓度（MIC）情况选择方案。     

Helicobacter pylori eradication in childhood after failure of initial treatment: advantage of quadruple therapy with nifuratel to furazolidone

BACKGROUND: Failures of Helicobacter pylori eradication in children are common. AIM: To evaluate the efficacy of amoxicillin, bismuth subcitrate and omeprazole and nifuratel or furazolidone for H. pylori eradication in children who failed initial treatment with a standard triple therapy. METHODS: Seventy-six consecutive H. pylori-positive paediatric out-patients (aged 12-16 years; mean age 13.7 +/- 1.4) with chronic abdominal complaints who had failed one attempt of eradication of H. pylori using metronidazole-containing triple therapy were enrolled. It was an open prospective study. Patients were randomized to receive a 2-week course of bismuth subcitrate (8 mg/kg/day, q.d.s.), amoxicillin (50 mg/kg/day, q.d.s.), with either nifuratel (15 mg/kg/day, q.d.s.) or furazolidone (10 mg/kg/day, q.d.s.), plus omeprazole (0.5 mg/kg, once daily). RESULTS: There were 37 patients in the nifuratel group and 39 in the furazolidone group. Helicobacter pylori was eradicated in 33 of 37 (89%; 95% CI: 74.5-96.9; intention-to-treat) in nifuratel group and in 34 of 39 (87%; 95% CI: 72.5-95.7) in furazolidone group, respectively. Frequency of severe side-effects was greater with furazolidone (21%) than with nifuratel (3%; P = 0.0289). CONCLUSIONS: Nitrofuran-containing therapies consisting of a proton-pump inhibitor, amoxicillin and bismuth citrate plus either nifuratel or furazolidone produced good cure rates even among those who had failed prior therapy. Nifuratel is preferred because of the lower frequency of side-effects.     

加替沙星与环丙沙星随机对照治疗细菌性感染

目的　以甲磺酸加替沙星氯化钠注射液和环丙沙星注射液随机对照治疗中、重度急、慢性呼吸道、泌尿道感染 ,评价甲磺酸加替沙星氯化钠注射液的疗效及安全性。方法　 2 5例患者接受甲磺酸加替沙星氯化钠注射液 2 0 0mg ,每日 2次 ;2 7例接受环丙沙星 2 0 0mg ,每日 2次 ,重者 3次 ,疗程 5～ 14d。结果　试验组和对照组痊愈率和有效率分别为 72 0 %、5 1 9% (P >0 0 5 )与 88 0 %、77 8% (P >0 0 5 )。两组的细菌阳性率、清除率分别为 68 0 %、74 1% (P >0 0 5 )和 94 4%、90 5 % (P >0 0 5 )。临床分离的 3 9株致病菌对甲磺酸加替沙星、环丙沙星、左氧氟沙星、司帕沙星、头孢噻肟的敏感率分别为 94 9%、84 6%、87 2 %、82 1%、89 7%。甲磺酸加替沙星的抗菌活性与左氧氟沙星、头孢噻肟相比差异无显著性 (P >0 0 5 ) ,但与环丙沙星、司帕沙星相比差异有显著性 (P <0 0 5 )。两组不良反应发生率分别为 11 5 %和 7 4% (P >0 0 5 )。结论　甲磺酸加替沙星氯化钠注射液治疗中、重度细菌感染安全、有效。     

甲泼尼龙与氢化可的松治疗腹型过敏性紫癜疗效比较

目的:比较甲泼尼龙琥珀酸钠与氢化可的松治疗腹型过敏性紫癜的疗效.方法:将90例过敏性紫癜患儿随机分为两组.治疗组给予静脉滴注甲泼尼龙琥珀酸钠2 mg/kg,q 12 h;对照组给予氢化可的松8 mg/kg, q 12 h,两组治疗3 d后观察并比较疗效.结果:治疗组总有效率为89.6%,对照组总有效率为66.7%,两组...     

蒙特卡洛模拟评价和优化鲍曼不动杆菌血流感染给药方案

目的 应用蒙特卡洛模拟研究头孢哌酮/舒巴坦、替加环素和多黏菌素B治疗鲍曼不动杆菌血流感染的疗效,预测和评价不同抗菌药物的抗菌效果,进而优化临床给药方案。方法 借助全国血流感染细菌耐药监测联盟(BRICS)平台收集2018—2019年血流感染来源的鲍曼不动杆菌514株,使用文献公开发表的头孢哌酮/舒巴坦、替加环素和多黏菌素B的药动学参数,基于药动学/药效学(PK/PD)理论利用蒙特卡洛模拟法,计算不同给药方案在各特定的MIC值获得的目标概率,即达标概率(PTA)和累积反应分数(CFR),以PTA或CFR≥90%作为临床疗效评价的指标。结果 治疗鲍曼不动杆菌引起的血流感染,头孢哌酮/舒巴坦给药方案4.5 g q6 h在最低抑菌浓度(MIC)≤1 mg/L时,可获得大于或接近90%的目标PTA值,临床分离菌的CFR值为21.53%。替加环素推荐剂量(50 mg q12 h),在MIC≤0.25 mg/L时,可获得大于90%的目标PTA值,100 mg q12 h的给药方案对临床菌株的CFR值为81.04%。多黏菌素B 1.25 mg/kg 1h输注q12 h给药方案,可使MIC≤1 mg/L...     

Pharmacokinetic/pharmacodynamic adequacy of polymyxin B against extensively drug-resistant Gram-negative bacteria in critically ill,general ward and cystic fibrosis patient populations

Dose-limiting nephrotoxicity is a significant side effect of polymyxin B treatment. Only limited clinical studies describe the pharmacodynamics of polymyxin B, with little guidance existing for treatment optimisation against multidrug-resistant Gram-negative bacteria. In this study, differences in the likelihood of achieving efficacious and toxic exposures of polymyxin B for critically ill, general ward and cystic fibrosis (CF) patients were evaluated. The following dosing regimens were tested: maintenance doses of 1, 1.25, 1.5 and 2 mg/kg every 12 h (q12h); and loading doses of 2 mg/kg followed by 1.25 mg/kg q12h and 2.5 mg/kg followed by 1.5 mg/kg q12h. Patient weight notably influenced exposure and the required patient dose. To achieve an optimised exposure with minimal toxicity risk, an empirical polymyxin B dose of 2 mg/kg q12h was required for critically ill patients weighing 50 kg, whereas doses of 1.25 mg/kg q12h and 1 mg/kg q12h were required for those weighing 75 kg and 100 kg, respectively. Conversely, 2 mg/kg q12h was required for general ward patients weighing 75 kg. For general ward and CF patients weighing 50 kg, the target exposure could not be achieved with any regimen. Furthermore, the likelihood of toxicity was always high for bacteria with minimum inhibitory concentrations (MICs) of ≥2 mg/L. These findings support the use of a loading dose to increase the achievement of polymyxin B target exposures. To improve efficacy, doses should be optimised according to the patient population.     

Moxalactam myoclonus, seizures, and encephalopathy

Severe myoclonus, generalized seizures, and marked stupor occurred in a 39-year-old woman with chronic renal insufficiency after one week of moxalactam 2 g iv q8h. Moxalactam serum levels far exceeded the recommended therapeutic range. The drug half-life was 17 hours (normal 1.9). Excessively high levels of moxalactam, which penetrates the blood-brain-barrier relatively easily, may provoke seizures and encephalopathy.     

Pharmacokinetic comparison of three clindamycin phosphate dosing schedules

In a randomized, three-way crossover study, six male volunteers received clindamycin phosphate 600 mg iv q6h (treatment A), 600 mg iv q8h (treatment B), or 900 mg iv q8h (treatment C). Plasma clindamycin concentrations were determined periodically for eight hours after achieving steady state. The results indicate that treatment C yielded significantly higher peak plasma clindamycin concentrations than treatments A or B. There were no significant differences in minimum plasma clindamycin concentrations (Cmin) or area under the plasma concentration versus time curve (AUC24) between treatments A and C. However, both treatments A and C yielded significantly greater Cmin and AUC24 values than treatment B. There were no significant differences among treatments for clindamycin clearance. It is concluded that clindamycin phosphate 900 mg q8h is a pharmacokinetically acceptable alternative to clindamycin phosphate 600 mg q6h.     

奥曲肽治疗慢性肾功能衰竭并发的上消化道出血

慢性肾功能衰竭合并胃镜证实消化道大出血７例（男性３例，女性４例；年龄５４±ｓ９ａ）。腹膜透析病人用奥曲肽０．１ｍｇ加２５％葡萄糖液２０ｍＬ，ｉｖ０．４－０．５ｍｇ加１０％葡萄糖液１０００ｍＬ，ｉｖｇｔｔ，２４ｈ，用至粪隐血阴性；血液透析病人用０．１ｍｇ加２５％葡萄糖液２０ｍＬ，ｉｖ，０．１ｍｇ，ｓｃ，ｑ８ｈ或ｑ１２ｈ，用至粪隐血阴性。全部止血成功，未见明显副作用。     

Toxicologic evaluation of injectable acemannan in the mouse, rat and dog.

Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4)-acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip-treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced.     

依诺沙星治疗感染性疾病的临床研究

依诺沙星(Enoxacin,ENX)是一种新的喹诺酮类抗菌剂,其抗菌谱广,口服吸收快,本文报道用ENX治疗各种细菌性感染101例,其中71例与诺氟沙星(Norfloxacin,NFX)治疗组60例作对照,年龄17～91岁(>65岁者8例),男70例,女91例,药物剂量均为0.3～0.6克每日三次,疗程7～14天,结果随机对照组ENX与NFX疗效各为94.37％,83.3％(P<0.05),有显著差异,其中对伤寒病治疗ENX优于NFX,两组细菌清除率各为95.5％,94.8％(P>0.05),无显著差异。不良反应各为9.86％和11.7％。ENX治疗各种细菌感染101例,有效率为96.0％,细菌清除率为95.8％,不良反应主要为消化道反应,另皮疹3例,白细胞及血小板下降各1例,未见肝肾功损害。体外抗菌活性表明ENX对肠杆菌科有高度的抗菌活性,包括对氨苄青霉素、庆大霉素、头孢唑林、氯霉素耐药菌均有较强的抗菌活性,对绿脓杆菌、金葡球菌及表葡球菌也有良好的抗菌作用,表明依诺沙星是一抗菌谱广、抗菌活性强、使用安全有效的抗菌药物。     

盐酸头孢吡肟治疗小儿下呼吸道感染87例疗效观察

目的评价头孢吡肟（Cefepim,FEP）治疗小儿下呼吸道感染的临床疗效。方法87例患者,分成治疗组46例和对照组41例,分别应用头孢吡肟和头孢地嗪,剂量均为50mg/（kg.d）,1次/12h,静脉滴注给药,疗程7～10d。结果头孢吡肟和头孢地嗪临床有效率分别为91.3%、87.8%,细菌清除率分别为91.0%、87.0%,不良反应发生率较低。结论头孢吡肟可作为治疗小儿下呼吸道感染有效和安全的抗生素。     

Cefoxitin in newborn infants

Fifteen patients less than 2 months old with bacterial infections caused by pathogens known or presumed to be sensitive to cefoxitin were studied. Cefoxitin was administered as an i.v. bolus injection over 15 min, every 8 h for 6 to 12 days, to a total daily dosage of 90 mg/kg. In 14 patients cefoxitin therapy resulted in eradication of the pathogen and in recovery from clinical signs of infection. Only one patient did not respond to cefoxitin therapy. No adverse clinical or haematological effects definitely caused by cefoxitin were observed. Plasma and urine samples collected after the first dose were assayed for cefoxitin by HPLC. Pharmacokinetic data indicated larger apparent volume of distribution (0.5 1/kg), a smaller plasma clearance (0.27 1/h/kg) and a longer half-life (1.43 h) than in adults. The plasma half-life was inversely correlated (p less than 0.05) to the postnatal age of the patients. Cefoxitin may be safely used in infants with infections caused by susceptible pathogens.     

Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem

Prolonging the infusion of meropenem over 3 hours increases the percentage of the dosing interval that drug concentrations remain above the minimum inhibitory concentration (MIC), thereby maximizing the pharmacodynamics of this agent and adhering to drug stability constraints. Monte Carlo simulation was employed to determine pharmacodynamic target attainment rates for several prolonged infusion (PI) meropenem dosage regimens as compared with the traditional 30-minute infusion (TI) against Enterobacteriaceae, Acinetobacter species, and Pseudomonas aeruginosa populations. Percent time above the MIC (%T>MIC) exposures for 1000 mg TI q8h, 2000 mg TI q8h, 500 mg PI q8h, 1000 mg PI q12h, 1000 mg PI q8h, 2000 mg PI q12h, and 2000 mg PI q8h were simulated for 10,000 subjects. Variability in pharmacokinetic parameters and MIC distributions were derived from studies in healthy volunteers and the MYSTIC surveillance program, respectively. The probabilities of attaining bacteriostatic (30% T>MIC) and bactericidal (50% T>MIC) exposures were high for all dosage regimens against populations of Enterobacteriaceae. Against Acinetobacter species and Pseudomonas aeruginosa, the 2000-mg PI q8h dosage regimen provided the highest target attainment rates. For mild to moderate infections caused by Enterobacteriaceae, prolonged infusion regimens of 500 mg PI q8h and 1000 mg PI q12h would provide equivalent target attainment rates to the traditional 30-minute infusion while requiring less drug over 24 hours. For more serious infections presumably caused by Acinetobacter species or Pseudomonas aeruginosa, a dose of 2000 mg PI q8h is recommended because of its high bactericidal target attainment rate against these pathogens. Further study of these dosage recommendations in clinical trials is suggested.     

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.     

Laboratory and clinical studies on cefdinir in pediatric field

Clinical trials of cefdinir (CFDN) in pediatric infections were carried out. Results are summarized as follows. 1. Mean half-lives of CFDN in serum in children when administered on an empty stomach were 1.24 hours (3 mg/kg per os) and 1.85 hours (6 mg/kg per os). 2. Mean 8 hour urinary excretion rates of CFDN were 19.0% (3 mg/kg/per os) and 10.5% (6 mg/kg per os). 3. CFDN was administered to 28 children with various infections: 12 patients with tonsillitis, 8 with bronchitis, 2 with pneumonia, 4 with urinary tract infections, 1 staphylococcal scalded skin syndrome and 1 with impetigo. The overall efficacy rate was 89.3%. 4. Diarrhea was noted in 1 patient. Abnormal laboratory test values encountered were eosinophilia in 2 patients, thrombocytosis in 1.     

诺氟沙星治疗伤寒213例

本文报道确诊伤寒213例,分3组进行治疗和临床观察。诺氟沙星组(0.0-1.2g/d口服)153例;诺氟沙星(用量同前组)+氨苄西林(6g/d静滴)组45例;诺氟沙星(用量同前)+庆大霉素(200-240mg/d静滴)组15例。疗程均为2-3wk。结果痊愈率分别为94.1％、96％和87％,3组之间无显著差异(P>0.05)。诺氟沙星治疗伤寒疗效优,副作用少而轻。