大肠埃希菌尿液分离株氨基糖苷类获得性耐药基因研究

大肠埃希菌是医院感染的常见病原菌,随着临床抗菌药物的大量使用,该菌不仅对喹诺酮类抗菌药物的耐药率明显上升,对氨基糖苷类药物的耐药问题也日趋严重,给临床抗感染治疗带来严峻挑战.有关对氨基糖苷类药物的耐药机制,传统观点认为是细菌产生一种或多种针对抗菌药物的氨基糖苷类修饰酶（AMEs）[1-2].     

Antibiotic related acute kidney injury in patients treated for open fractures

ObjectiveAntibiotic administration during the treatment of open fractures has been shown to reduce infection rates and is considered a critical step in the management of these injuries. The purpose of this study was to determine if aminoglycoside administration during the treatment of open fractures leads to acute kidney injury.MethodsPatient records at a level I trauma centre were reviewed for adult patients who presented in 2014 with open fractures were screened for inclusion. Patients were excluded with fractures of the phalanges, metatarsals, and metacarpals, with isolated traumatic arthrotomies, or pre-existing renal dysfunction. Charts were reviewed for patient age, gender, race, past medical history, medication history, injury severity score, intravenous dye studies and fracture type. Patients were divided into those given cefazolin (Group A) and cefazolin with gentamicin (Group B). Laboratory values were used to determine which patients developed kidney dysfunction as measured using the RIFLE criteria. Wilcoxon–Mann–Whitney test and Chi-square were used to compare interval and categorical variables, respectively. Significance was set at P < 0.05.ResultsOne-hundred and fifty-nine patients met inclusion criteria. Forty-one (25%) patients were given cefazolin alone and 113 (68%) patients were given cefazolin with gentamicin. Ten (18%) patients with Gustilo-Anderson type III fractures were given cefazolin alone and 67 (67%) patients with types I or II fractures were given a cefazolin with gentamicin. Baseline characteristics and risk factors for renal dysfunction did not vary between groups. Two (4.8%) patients in Group A and 5 (4%) patients in Group B developed acute kidney injury (P = 0.599).ConclusionsGentamicin use during the treatment of open fractures does not lead to increased rates of renal dysfunction when used in patients with normal baseline renal function.     

耐阿米卡星铜绿假单胞菌氨基糖苷类耐药基因及其基因型研究

目的了解耐阿米卡星(AMK)铜绿假单胞菌(Pa)的氨基糖苷类修饰酶基因和氨基糖苷耐药基因的存在情况及其基因型。方法对临床分离的72株多重耐药Pa(其中对AMK耐药Pa组和对AMK敏感Pa组各36株)分别用聚合酶链反应(PCR)测定9种主要的氨基糖苷类修饰酶基因和2种氨基糖苷耐药基因,用基因外重复回文序列(REP)-PCR进行基因型研究。结果在分组研究中AMK耐药Pa组表现为aac(6′)-Ⅰ和aac(3)-Ⅱ基因同时阳性的占42.4%,aac(6′)-Ⅰ和ant(2″)-Ⅰ基因同时阳性的占36.4%,是耐药组的主要修饰酶基因;AMK敏感Pa组表现为aac(6′)-Ⅰ基因阳性的占50.0%,aac(3)-Ⅱ基因阳性的占33.2%,是敏感组的主要修饰酶基因。2种氨基糖苷耐药基因(RmtA和RmtD)均为阴性。REP-PCR显示耐药菌株可分为A～G 7型,其中AMK耐药Pa组的主要分型为F型(其中尤以F1型为多);AMK敏感Pa组以E型为多见。结论通过2种或多种氨基糖苷类修饰酶同时作用于AMK是Pa对AMK耐药的重要途径之一。     

革兰阴性杆菌16S rRNA甲基化酶基因检测及作用研究

目的分析上海中医药大学附属普陀医院临床分离的革兰阴性杆菌中16S rRNA甲基化酶基因的流行情况及革兰阴性杆菌的氨基糖苷类耐药机制。方法收集临床分离的对阿米卡星和/或庆大霉素耐药的革兰阴性杆菌53株。采用聚合酶链反应（PCR）法检测16S rRNA甲基化酶基因：armA、rmtA、rmtB、rmtC、rmtD、npmA;PCR阳性产物测序分析。构建PET32-armA和PET32-rmtB的重组质粒并转化入宿主菌BL21中。纸片扩散法（K-B）检测临床分离16S rRNA甲基化酶基因阳性菌株和重组菌对5种氨基糖苷类药物的敏感性。结果 53株耐药菌中5株鲍曼不动杆菌、2株肺炎克雷伯和1株阴沟肠杆菌检出armA基因,2株大肠埃希菌检出rmtB基因。获得PET32-armA和PET32-rmtB的重组BL21菌株。PET32-armA和PET32-rmtB的重组菌均获得氨基糖苷类抗菌药物耐药性。结论本院临床样本检测到16S rRNA甲基化酶基因armA和rmtB阳性菌株,armA基因存在于鲍曼不动杆菌、肺炎克雷伯菌和阴沟肠杆菌中;rmtB基因位于大肠埃希菌中。将armA和rmtB基因转入非耐药的宿主菌中可以诱导其对氨基糖苷类抗菌药物的耐药。     

氨基糖苷类抗生素M—41—A的分离和鉴别

从橄榄星孢小单孢菌M－41的发酵液中分离到氨基糖苷类抗生素M－41－A,基于理化性质和光谱数据,抗生素M－41－A已鉴别为Verdamicin。     

Aminoglycoside ototoxicity: a human temporal bone study.

OBJECTIVE: Hearing loss after aminoglycoside administration has been thought to result primarily from hair cell injury. The purpose of the study was to determine the potential for direct injury of spiral ganglion cells and hair cells in cases of documented human aminoglycoside ototoxicity. STUDY DESIGN: Retrospective case review. METHODS: The clinical course of two individuals with aminoglycoside ototoxicity are documented, including the details of administration of tobramycin and other ototoxic medication and serial audiograms. The temporal bones were processed, and the cochlear elements quantified. RESULTS: Histopathological study of the temporal bones from the individuals in the study demonstrated reduction of both ganglion cell and hair cell populations. Spiral ganglion cell loss was not necessarily subadjacent to areas of hair cell loss in cases of aminoglycoside ototoxicity. Instead, spiral ganglion cell reduction may be present in segments of the cochlea with normal-appearing hair cells. CONCLUSIONS: The study suggests that aminoglycoside antibiotics can injure spiral ganglion cells directly, as well as hair cells. Thus, the characteristic hearing loss of ototoxicity can result from degeneration of either cochlear element.     

Neuromuscular blockade induced by flunarizine alone and in combination with pancuronium, suxamethonium or neomycin: studies in isolated rat phrenic-hemidiaphragm preparations

The in vitro effects of flunarizine on indirectly- and directly-elicited contractions in rat phrenic-hemidiaphragm preparations were studied. The interactions of flunarizine with non-depolarizing and depolarizing neuromuscular blocking drugs (pancuronium and suxamethonium) and with an aminoglycoside antibiotic (neomycin) were also evaluated. Flunarizine induced a slowly developing concentration-dependent reduction of indirectly-elicited diaphragm twitch height, but only slightly reduced directly-elicited contractions. Flunarizine 1 and 5 mumol.l-1 produced a concentration-dependent enhancement of pancuronium-induced neuromuscular blockade, whereas suxamethonium blockade was significantly increased by flunarizine 5 mumols.l.-1 only. Moreover, both flunarizine 1 and 5 mumols.l-1 also increased the neuromuscular blockade induced by neomycin. In conclusion, flunarizine induced neuromuscular blockade and enhanced the effects of several neuromuscular blocking agents to varying degrees in vitro.     

Oral administration of geranylgeranylacetone to protect vestibular hair cells

Objective

We recently reported that the heat shock response played a major role in the protection of hair cells against stress. Oral administration of the heat shock inducer, geranylgeranylacetone (GGA) protected hair cells against intense noise. In our present study, we investigated the effect of GGA on vestibular hair cell death induced by an aminoglycoside.

Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside treatment

Although aminoglycosides have been investigated for their cochleotoxicity, it has still not been determined whether apoptosis or necrosis results in cochlear hair cell death following aminoglycoside treatment. To study possible mechanisms of cell death, we used in situ DNA break-labeling to examine guinea pig cochleae affected by kanamycin ototoxicity. Chronic kanamycin treatment induced DNA fragmentation that was detectable in both outer and inner hair cells, suggesting the occurrence of apoptosis. These findings suggest that apoptosis achieves deletion of affected hair cells without disrupting tissue architecture in the organ of Corti. Received: 22 April 1997 / Accepted: 31 July 1997