奈替米星与阿米卡星治疗下呼吸道感染的临床疗效比较

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。方法共入选病例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。安全性评价入选病例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％，敏感茵百分率分别为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。     

氧氟沙星联合丁胺卡那霉素治疗耐多药肺结核的疗效分析

目的观察氧氟沙星联合丁胺卡那霉素在治疗耐多药肺结核治疗中的作用。方法将耐多药肺结核患者71例随机分为2组:治疗组(38例)采用卡那霉素联合利福平、结核清及吡嗪酰胺、乙胺丁醇,疗程18个月。结果患者完成化疗疗程时;治疗组痰菌阴转率89.5%,优于对照组54.5%,(P<0.01);治疗组病灶吸收率94.7%,优于对照组57.5%,治疗组空洞闭合率71.9%,也优于对照组35.3%,(P<0.05)。结论氧氟沙星联合丁胺卡那霉素治疗耐多药肺结核痰阴转高,病变吸收好,药物不良反应低,值得在临床上推广应用。     

阿米卡星在严重败血症患者体内的药代动力学研究

目的：初步探讨25 mg·kg －1的阿米卡星在重症监护室（ICU）患者体内的药代动力学。方法纳入符合条件的30例革兰阴性（G －）败血症患者进行阿米卡星药物治疗研究,通过非房室模型计算每名患者的阿米卡星的药代动力学。结果阿米卡星在 G －败血症患者体内平均药物分布为（0．36±0．07）L·kg －1,平均血液清除率为（3．88±0．97）mL·min －1·kg －1。肌酐清除率与血清肌酸酐（SCr）相关性具有统计学意义。结论对 ICU 患者应用高剂量阿米卡星（≥25 mg·kg －1）需要考虑败血症对血液动力学的影响,需要密切监测败血症血液药物浓度变化,关键要考虑到重症患者体内药代动力学与普通人群是不同的。     

Amikacin-induced acute renal injury in rats: protective role of melatonin

It is well established that some agents such as aminoglycosides generate free oxygen radicals, leading to an increased oxireductase production, which in turn increases tissue toxicity. The aim of this study is to test whether melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant and free radical scavenger, reduces the nephrotoxicity caused by amikacin (AK). Herein, we investigated the physiologic and pharmacological role of melatonin in influencing AK-induced nephrotoxicity. For this, pinealectomized (Px) and sham operated (non-Px) rats were used. Both AK and melatonin were administered to all groups. We investigated the effects of melatonin on AK-induced changes in levels of malondialdehyde (MDA), a lipid peroxidation product, glutathione (GSH), an antioxidant whose levels are influenced by oxidative stress, and blood urea nitrogen (BUN) and serum creatine (Cr) levels. Morphologic changes in the kidney were also examined by using light microscopy. MDA levels were found to be higher in Px than in non-Px AK-treated animals. Melatonin administration to Px rats reduced MDA levels. In relative to non-Px rats, Px animals treated with AK had significantly lower GSH concentrations while melatonin administration elevated GSH levels in the kidney; however, this stimulatory effect of melatonin was not observed in non-Px AK-treated rats. Treatment with AK alone resulted in significantly higher plasma Cr and BUN levels. Repeated administration of melatonin prevented the AK-induced elevation of plasma Cr and BUN levels. Morphologic damage to renal tubules as a result of AK was more severe in the renal cortex than in the medulla. The damage to the kidney induced by AK was reversed by melatonin in the Px rats. In conclusion, these results show that physiologic melatonin concentrations are important in reducing AK-induced renal damage, while pharmacologic concentrations of melatonin did not add to the beneficial effect.     

Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin

Background and objective: Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient’s glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N‐acetyl‐β‐ d glucosaminidase (NAG), creatinine level and creatinine clearance]. Methods: We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft–Gault formula) and CyC (Grubb’s formula). Seventy‐one patients (mean age 12 years; range 4–28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U‐NAG/U‐creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy. Results: Significant differences in the rate of U‐NAG/U‐creatinine were noted before and after treatment with amikacin (P < 0·001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0·001), and CyC clearance showed a significant decrease (P < 0·001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased. Conclusion: We showed that the rate of U‐NAG/U‐creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.     

Persistence of the otoprotective effect. How long does otoprotection against amikacin lasts?

There is evidence that a “resistance phenomenon” occurs when a none-damaging dose of amikacin protects the hair cells from ototoxicity. Our goal is to prove that this resistance is persistent.MethodExperimental study - 14 albino guinea pigs (Cavia porcellus) divided into three groups. The auditory function was assessed by distortion product otoacoustic emissions (DPOAE): before exposure to amikacin, on the 15th day after the non-damaging dose was injected, at the end of the damage dose injection and prior to decapitation.ResultsGroup A (control) presented normal hearing and histological pattern. Group B (amikacin 20 mg/kg/day (IM) for 30 days and affecting dose (400 mg/kg/day) for 12 days and Group C (same protocol of Group B, but kept for 60 days and slaughtered), the DPOAE confirmed normal auditory function in the pre-exposure and maintenance of the standard-dose; however, significant loss of auditory function after the end of the damaging dose injection.ConclusionThe protection phenomenon did not extended for a period of 30 to 60 days after the application of damaging doses of amykacin.     

阿米卡星对豚鼠耳蜗毛细胞的损伤作用

目的研究阿米卡星（amikacin,AMK）在不同给药时间内对豚鼠耳蜗毛细胞的损伤作用,探讨AMK的耳毒性。方法豚鼠随机分为对照组、AMK3d组、AMK7d组和AMK11d组。采用异硫氰酸四甲基罗丹明标记的鬼笔环肽荧光染色方法,并结合听脑干反应（auditory brainstem response,ABR）测试,观察用药前后耳蜗毛细胞形态及听功能的改变。结果AMK首先损伤耳蜗底回的外毛细胞,并且随着给药时间延长,损伤逐渐向顶回发展,外毛细胞缺失明显增多,而AMK对内毛细胞的损伤要轻于外毛细胞。听功能改变与形态学变化基本一致。结论AMK可损伤豚鼠耳蜗毛细胞,导致听功能下降。     

Delivering antibiotics to the lungs of patients with ventilator-associated pneumonia: an update

Ventilator-associated pneumonia is a serious hospital-acquired infection, with 20–70% crude mortality and 10–40% estimated attributable mortality. Insufficient antibiotic concentrations at the infection site when these drugs are given intravenously may lead to poor outcomes, particularly when difficult-to-treat pathogens are responsible; for example, Pseudomonas aeruginosa, extended spectrum beta lactamase-producing Gram-negative bacilli, Acinetobacter spp. and/or methicillin-resistant Staphylococcus aureus. Direct drug delivery to the infection site via aerosolization combined with intravenous administration achieves concentrations exceeding MICs of the pathogens, even those with impaired susceptibility. Experimental and recent clinical results demonstrated our markedly improved ability to deliver aerosolized antibiotics to the lung with new-generation devices, for example, vibrating-mesh nebulizers. Convincing clinical data from a large randomized trial are still lacking to support the routine administration of aerosolized antibiotics to treat ventilator-associated pneumonia, even though some small-randomized trials’ observations are encouraging.     

Evaluation of population pharmacokinetic models for amikacin dosage individualization in critically ill patients

Objectives The aim of this study was to evaluate the reliability for dosage individualization and Bayesian adaptive control of several literature‐retrieved amikacin population pharmacokinetic models in patients who were critically ill. Methods Four population pharmacokinetic models, three of them customized for critically‐ill patients, were applied using pharmacokinetic software to fifty‐one adult patients on conventional amikacin therapy admitted to the intensive care unit. An estimation of patient‐specific pharmacokinetic parameters for each model was obtained by retrospective analysis of the amikacin serum concentrations measured (n = 162) and different clinical covariates. The model performance for a priori estimation of the area under the serum concentration‐time curve (AUC) and maximum serum drug concentration (C_max) targets was obtained. Key findings Our results provided valuable confirmation of the clinical importance of the choice of population pharmacokinetic models when selecting amikacin dosages for patients who are critically ill. Significant differences in model performance were especially evident when only information concerning clinical covariates was used for dosage individualization and over the two most critical determinants of clinical efficacy of amikacin i.e. the AUC and C_max values. Conclusions Only a single amikacin serum level seemed necessary to diminish the influence of population model on dosage individualization.     

苯唑青霉素对丁胺卡那毒素药动学的影响

 采用微量微生物法对丁胺卡那霉素（AMK）单用及AMK与苯唑青霉素（OXA）合用后，兔体内AMK血药浓度进行测定；药时数据用MCPKP软件经IBM计算机处理，并对两组药动学参数进行了统计学处理，结果表明OXA对AMK的药动学有显著的影响。