Chronopharmacokinetics of Imipenem in the Rat

There are no studies indicating a possible modification of imipenem pharmacokinetics related to the hour (i.e., circadian time) of its administration. The aim of this study was to evaluate the influence of different times of intramuscular imipenem administration on its disposition in Wistar AF EOPS rats. Four groups of eight animals were given a single intramuscular injection of 140 mg/kg of imipenem either at 10∶00, 16∶00, 22∶00, or 04∶00 h. Blood samples were collected 0.5, 1, 2, 3, 4, 6, and 8 h after drug injection, and the main pharmacokinetic parameters determined were C_max, T_max, elimination half‐life (t_1/2), area under the concentration‐versus‐time curve (AUC), total serum clearance (CL/F), and volume of distribution (V/F). Circadian variation of C_max (49%), T_max (92%), and AUC (19%) was observed leading to variability of imipenem exposure. Clearance and volume of distribution were modified according to the circadian time of drug injection but did not reach statistical significance. The results suggest that varying the time of administration induces intra‐individual variability.     

Imipenem and expression of multidrug efflux pump in Enterobacter aerogenes

Imipenem is often used to treat intensive care unit patients infected by Enterobacter aerogenes, but it is leading to an increasing number of antibiotic resistant strains. Clinical isolates and imipenem resistant variants presented a high level of resistance to beta-lactam antibiotic group and to chemically unrelated drugs. We report here that imipenem selects strains which contain active efflux pumps ejecting various unrelated antibiotics including quinolones, tetracycline, and chloramphenicol. An increase of AcrA, an efflux pump component, was observed in the imipenem resistant variants. The overexpression of marA, involved in the genetic control of membrane permeability via porin and efflux pump expression, indicated the activation of the resistance genetic cascade in imipenem resistant variants.     

Prevalence of multidrug resistant and extended spectrum beta-lactamase producing Pseudomonas aeruginosa in a tertiary care hospital

Resistance to broad-spectrum beta-lactams, mediated by extended-spectrum beta-lactamase enzymes (ESBL), is an increasing problem worldwide. The present study was undertaken to determine the incidence of ESBL-production among the clinical isolates of Pseudomonas aeruginosa and their susceptibility to selected antimicrobials. A total of one eighty-seven clinical specimens were tested for the presence of ESBL production using the double-disc synergy test. Of these, 25.13% (n = 47) isolates of P. aeruginosa were observed as ESBL positive. The maximum number of ESBL-producing strains were found in sputum (41.67%; n = 24) followed by pus (28.36%; n = 19), cerebrospinal fluid and other body fluids (21.74%; n = 5), urine (20.45%; n = 9) and blood (13.79%; n = 4). ESBL producing isolates exhibited co-resistance to an array of antibiotics tested. Imipenem and meropenem can be suggested as the drugs of choice in our study.     

Antimicrobial activities of Saudi honey against Pseudomonas aeruginosa

Five types of imported and local honey were screened for both their bacteriocidal/bacteriostatic activities against both Imipenem resistant and sensitive Pseudomonas aeruginosa in both Brain Heart infusion broth and Mueller–Hinton agar. The results indicated that the effect was concentration and type of honey dependant. All types of honey tested exerted a full inhibition of bacterial growth at the highest concentration tested of 50% at 24 h of contact. The inhibitory effect of honey on bacterial growth was clear with concentrations of 20% and 10% and this effect was most evident in the case of Manuka honey as compared to Nigella sativa honey and Seder honey. Manuka honey UMF +20 showed a bacteriocidal activity on both Imipenem resistant and sensitive P. aeruginosa, while Seder honey and N. sativa honey exerted only a bacteriostatic effect. Manuka honey UMF +10 showed most effect on antimicrobial resistance. Manuka honey UMF +10 had an effect on modulation of Imipenem resistant P. aeruginosa. Conclusion: The results indicated that various types of honey affected the test organisms differently. Modulation of antimicrobial resistance was seen in the case Manuka honey UMF +10.     

2007-2010四年间鲍曼不动杆菌耐药性变迁及对亚胺培南耐药的机制研究

目的研究2007-2010四年间中山大学附属第一医院临床分离的鲍曼不动杆菌的耐药性迁移情况和耐亚胺培南的鲍曼不动杆菌(IRAB)的耐药机制,为临床抗感染治疗提供依据。方法采用VITEK 2型全自动微生物检测系统对细菌进行鉴定及药敏分析;用PCR方法检测碳青霉烯酶基因blaOXA-51、blaOXA-23、blaOXA-24和blaOXA-58。结果 2007-2010四年间分离鲍曼不动杆菌811株,耐药率逐年上升,其对头孢哌酮/舒巴坦、美罗培南、头孢吡肟、亚胺培南和哌拉西林/他唑巴坦的耐药率上升明显,如对亚胺培南的耐药率自2007-2010年分别为13.1%、26.0%、44.3%和59.5%。811株鲍曼不动杆菌中IRAB有311株,IRAB对抗生素的耐药率明显升高,但四年间的耐药率变化并不明显。对IRAB敏感的抗生素以阿米卡星为首,其次为头孢哌酮/舒巴坦,但头孢哌酮/舒巴坦的敏感率逐年下降。从311株IRAB中随机抽取140株,检出blaOXA-51基因阳性125株(89.3%),blaOXA-23基因阳性29株(20.7%),blaOXA-24基因阳性3株(2.14%),blaOXA-58基因阳性22株(15.7%)。结论鲍曼不动杆菌的耐药性逐年升高,以阿米卡星与头孢哌酮/舒巴坦联合应用为有效的治疗方法,产碳青霉烯酶是IRAB的主要耐药机制。     

Induction of axenic culture of Arthrospira (Spirulina) platensis based on antibiotic sensitivity of contaminating bacteria

Arthrospira platensis SAG 21.99 and the isolated bacteria (Halomonas spp., Staphylococcus sp., etc.) from the culture of A. platensis SAG 21.99 were treated with five antibiotics to determine the minimal lethal concentrations. The combination of a washing step and a consecutive treatment with antibiotics, imipenem (100 μg ml⁻¹), neomycin (100 μg ml⁻¹) and cycloheximide (20 μg ml⁻¹), treatment step was highly effective in eliminating bacteria. An axenic culture of A. platensis SAG 21.99 could be induced within 3 days using this method. This technique is a simple and rapid method for obtaining axenic cultures of filamentous cyanobacteria.     

164株阴沟肠杆菌的药物敏感性分析

目的了解阴沟肠杆菌的药物敏感性情况以指导临床合理用药。方法对中山大学附属第一医院近3年分离出的阴沟肠杆菌的标本分布及耐药情况进行回顾性分析。结果共分离出164株阴沟肠杆菌,其对亚胺培南、头孢吡肟、阿米卡星和氧氟沙星的敏感性较高。结论阴沟肠杆菌对3代头孢菌素耐药严重,呈多重耐药性,亚胺培南仍为治疗阴沟肠杆菌严重感染的首选用药。     

感染耐亚胺培南鲍曼不动杆菌临床分布情况及耐药性分析

目的:探讨感染耐亚胺培南(IPM)鲍曼不动杆菌临床分布情况及耐药性。方法:回顾性分析2013~2015年榆林市中医院患者感染鲍曼不动杆菌的临床分布,并对耐亚胺培南鲍曼不动杆菌进行培养、鉴定及药敏试验,分析其耐药情况。结果:2013~2015年我院共分离培养出鲍曼不动杆菌185株,其中IPM耐药99株(53.51%),IPM敏感86株(46.49%)。绝大部分菌株分离自痰液标本(138株,74.59%),其次是血液标本(14株,7.57%)与尿液标本(12株,6.49%);来自ICU送检标本菌株数量最多(84株,45.41%),其次是呼吸内科标本(53株,28.65%)与神经内科标本(30株,16.22%)。不同标本类型及科室中IPM耐药及IPM敏感鲍曼不动杆菌占比无显著差异(P0.05)。IPM耐药鲍曼不动杆菌对抗菌药物耐药性均较高,其中以头孢哌酮/舒巴坦(CSL)敏感性最高(50.51%);IPM敏感鲍曼不动杆菌对部分抗菌药物耐药性尚可,其中以IPM敏感性最高(93.02%)。结论:耐亚胺培南鲍曼不动杆菌临床分布广泛,多重耐药性严重甚至出现泛耐药,应当对患者进行药敏试验,以药敏结果选择合适的抗菌药物进行使用。     

奇异变形杆菌耐药性及亚胺培南不敏感株感染的临床特点研究

目的研究奇异变形杆菌的临床分布和耐药情况、亚胺培南不敏感奇异变形杆菌感染的临床特点。方法分析浙江大学医学院附属第一医院2013年1月至2013年12月分离的非重复奇异变形杆菌的药物敏感性、临床分布,回顾性分析亚胺培南不敏感奇异变形杆菌感染患者的临床资料、治疗及预后情况。结果2013年该院共分离107株奇异变形杆菌,以分离自尿液最多,其次为痰液;来源最多的是外科病房和重症监护病房。体外药敏显示：奇异变形杆菌对美罗培南、厄他培南、头孢吡肟、氨曲南、哌拉西林/他唑巴坦、头孢他啶、头孢哌酮/舒巴坦、阿米卡星等抗菌药物敏感性良好,敏感率达85%以上;对亚胺培南敏感率为80.4%;对头孢呋辛、环丙沙星、氨苄西林、头孢曲松、庆大霉素耐药率较高,超过30%;对呋喃妥因耐药率为99%。其中21株亚胺培南不敏感奇异变形杆菌对包括美罗培南、厄他培南在内的其他各类抗菌药物耐药率与亚胺培南敏感株基本相仿。亚胺培南不敏感奇异变形杆菌引起院内获得性感染主要发生在入住ICU、外科术后、广谱抗菌药物使用后、留置各类置管和梗阻性尿路疾病的患者,可引起泌尿系统、皮肤创面、腹腔、血流、生殖道等部位感染,表现为全身炎症反应及局部感染症状。选择敏感抗菌药物治疗后该部分患者预后良好。结论奇异变形杆菌对三、四代头孢菌素,β-内酰胺酶抑制剂合剂等抗生素敏感性良好。亚胺培南不敏感奇异变形杆菌对其他碳青酶烯类抗生素仍保持较高的敏感性。亚胺培南不敏感奇异变形杆菌所引起院内获得性感染主要发生在入住ICU、外科术后、广谱抗菌药物使用后、留置各类置管和梗阻性尿路疾病的患者,预后良好。     

Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®

β-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C β-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C β-lactamases in vitro. It effectively restored imipenem’s activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin® is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections.