Performance of a dosage individualization table for extended interval gentamicin in neonates beyond the first week of life

Objective: To assess the performance of a gentamicin dosing table for the individualization of extended-interval dosing (EID) in a neonatal population >7 days old.

Methods: A prospective observational study was carried out on gentamicin concentrations achieved using a dosing table in neonates >7 days old. Neonates were given 5?mg/kg IV gentamicin; then a table using 22?h post-first dose gentamicin concentrations was used to individualize dosing intervals. Pre- and post-serum gentamicin concentrations were measured and used to calculate the true peak and trough concentrations achieved.

Results: Use of the table resulted in dosing intervals that provided appropriate peak (mean 9.8?±?1.8?mg/L) and trough (mean 0.6?±?0.3?mg/L) concentrations in all neonates (n?=?38). All trough concentrations were <2?mg/L, 83% were <1?mg/L. The majority of peak concentrations were in the usual target range (87%, 5–12?mg/L), with a few being in a higher, although likely safe range (13%, 12.1–15.7?mg/L).

Conclusions: Use of this dosing table to individualize extended-interval gentamicin dosages in neonates >7 days old resulted in appropriate peak and trough concentrations in all neonates studied. This allows appropriate extended-interval aminoglycoside dosages in neonates early in treatment.     

表皮葡萄球菌icaADBC操纵子检出与细菌耐氨基糖苷类抗菌药物的关系

目的分析临床分离表皮葡萄球菌对不同类型氨基糖苷类抗菌药物的耐药特征;分析icaADBC操纵子在临床分离的表皮葡萄球菌中的检出及与细菌耐药的关系。方法收集2013年1~10月上海市东方医院临床分离的表皮葡萄球菌77株,采用纸片扩散法检测细菌4种氨基糖苷类抗菌药物(庆大霉素、链霉素、奈替米星和阿米卡星)药敏试验特征;构建icaADBC特异性引物,采用聚合酶链反应扩增技术检测77株细菌中icaADBC的分布状况。结果结果77株表皮葡萄球菌对氨基糖苷类抗菌药物耐药率较高,分别为庆大霉素:62.3%,链霉素:61.0%,阿米卡星:22.1%,奈替米星:23.4%。icaADBC操纵子的检出率为20.8%,ica阳性菌株与阴性菌株对氨基糖苷类抗菌药物耐药性比较差异有统计学意义(P0.05)。结论临床分离的icaADBC操纵子阳性表皮葡萄球菌对氨基糖苷类抗菌药物耐药率较高。     

Combination of Ofloxacin and Other Antimicrobial Agents

Summary

We evaluated the combination of ofloxacin with piperacillin, gentamicin, vancomycin, rifampin, clindamycin, and metronidazole by the checkerboard agar dilution method against 165 isolates which included Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa, Providencia stuartii, Acinetobacter, Staphylococcus aureus, Bacteroides fragilis, and Citrobacter perfringens. Synergy of piperacillin-ofloxacin was demonstrated for 50% and 40% respectively of E. cloacae and P. aeruginosa. Some ofloxacin and piperacillin-resistant isolates were susceptible with the combination. Ofloxacin-gentamicin was indifferent for aerobic gram-negative species. Ofloxacin and vancomycin or gentamicin was indifferent for S. aureus and E. faecalis, but rifampin-ofloxacin showed addition. Combination of ofloxacin and metronidazole or clindamycin or erythromycin was indifferent for aerobic and anaerobic species.

Ofloxacin could be combined with piperacillin with benefit against P. aeruginosa, but combination with aminoglycosides is not of benefit.     

16S rRNA Methyltransferase RmtC in Salmonella enterica Serovar Virchow

We screened Salmonella and Escherichia coli isolates, collected 2004–2008 in the United Kingdom, for 16S rRNA methyltransferases. rmtC was identified in S. enterica serovar Virchow isolates from clinical samples and food. All isolates were clonally related and bore the rmtC gene on the bacterial chromosome. Surveillance for and research on these resistance determinants are essential.     

一株多重耐药铜绿假单胞菌耐药基因的研究

目的：研究铜绿假单胞菌多重耐药情况和相关机制。方法：采用聚合酶链式反应（PCR）法对一株多重耐药铜绿假单胞菌进行β-内酰胺酶基因、氨基糖苷类修饰酶基因、氯霉素类基因、耐消毒剂和磺胺类基因检测。结果：PCR结果显示该株PA的TEM,MIR,CTX-M1群,OXA-1群,OXA-10群,aac（6′）-b,aac（6′）-,aac（3）-,ant（2″）-,catB,qacE△1-sul1基因均为阳性,GES,DHA,VEB,cmlA基因均阴性,Opr D2未缺失。结论：该株铜绿假单胞菌存在多重耐药基因,而且对胺类、胍类消毒剂耐受。     

Pharmacokinetics of Aminoglycosides

The Pharmacokinetics informations of aminoglycosides, their monograph and clinical Pharmacokinetics parameters are reported in this review. The Aminoglycosides are highly polarity and in reserve for serious infections caused by aerobic gram-negative bacteria and some gram-positive bacteria but their toxicity are major limitations in clinical use.     

亚胺培南对粒细胞减少症合并感染病人的疗效

目的探讨亚胺培南／西司他丁（泰能组）单用及头孢三代并阿米卡星（联合组）对粒细胞减少症合并感染病人的治疗效果，指导对此类病人的临床用药。②方法回顾性分析１３４例粒细胞减少症病人应用两组药物的有效率及细菌清除率。③结果泰能组有效５９例（８９％），联合组为５０例（７３％），二者比较差异有显著性（χ２＝３１．９２，Ｐ＜０．００５）；泰能组和联合组对革兰阳性细菌清除率分别为８７％和７２％，两者比较差异有显著性（χ２＝１１５．５４，Ｐ＜０．００５）；对革兰阴性细菌清除率分别为８４％和７５％，两者比较差异无显著性（χ２＝２．９２，Ｐ＞０．０５）；两组总细菌清除率分别为８６％和７３％，两者比较差异有显著性（χ２＝６３．８９．Ｐ＜０．００５）。联合用药无效者换用泰能有效率为７８％（１４／１８），泰能无效组改用联合用药者均无效。④结论泰能疗效优于头孢三代并阿米卡星，联合用药无效者应用泰能仍有较好疗效。     

Gentamicin-induced apoptosis in renal cell lines and embryonic rat fibroblasts.

Gentamicin, an aminoglycoside antibiotic, induces apoptosis in the proximal tubule epithelium of rats treated at low, therapeutically relevant doses (El Mouedden et al., Antimicrob. Agents Chemother. 44, 665-675, 2000). Renal cell lines (LLC-PK(1) and MDCK-cells) have been used to further characterize and quantitate this process (electron microscopy; terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling of fragmented DNA [TUNEL]; and DNA size analysis [oligonucleosomal laddering]). Cells were exposed for up to 4 days to gentamicin concentrations of up to 3 mM. Apoptosis developed, almost linearly, with time and drug concentration, and was (i) preventable within the time-frame of the experiments by overexpression of the anti-apoptotic protein Bcl-2, and by co-incubation with cycloheximide (MDKC but not LLC-PK(1) cells); (ii) associated with an increased activity of caspases (MDCK cells; bcl-2 transfectants showed no increase of caspase activities and Z-VAD.fmk afforded full protection). Gentamicin-induced apoptosis also developed to a similar extent in embryonic fibroblasts cultured under the same conditions. In the 3 cell types, apoptosis (measured after 4 days) was directly correlated with cell gentamicin content (apoptotic index [approximately 10 to 18% of TUNEL (+) cells for a content of 20 microg of gentamicin/mg protein; kidney cortex of rats showing apoptosis in proximal tubule epithelium typically contains approximately 10 microg of gentamicin/mg protein). Thus, gentamicin has an intrinsic capability of inducing apoptosis in eucaryotic cells. Development of apoptosis in proximal tubules of kidney cortex in vivo after gentamicin systemic administration is therefore probably related to its capacity to concentrate in this epithelium after systemic administration.     

Investigational therapies for the treatment of spinal muscular atrophy

Introduction: Currently, there is no cure available for the hereditary neurodegenerative disease proximal spinal muscular atrophy (SMA), which is the number one genetic killer in early childhood. However, growing knowledge of SMA pathophysiology has opened new avenues for potential therapeutic interventions.

Areas covered: This review summarizes a variety of investigational therapeutic approaches for SMA. Focusing on the current state-of-the-art applications, the authors discuss the outcome of the first clinical interventions and compare the first results from the newest strategies. The achievements of the investigational drugs highlighted in this article were deduced from original articles, pharmaceutical company press releases and clinical trial results.

Expert opinion: Nearly two decades after the discovery of the disease causing gene survival motor neuron 1, many therapeutic options for SMA have been developed, some of which made it to clinical trials but could not prove their promising experimental results. Recently, big research efforts from academia, government and the pharmaceutical industry have led to the development of highly promising compounds that are currently in clinical trials, and which could lead to feasible treatment options in the future.