不同pH值对大环内酯类药物抗肺炎支原体活性的影响

目的研究肺炎支原体（Mp）对大环内酯类药物的敏感性和耐药性以及不同pH值对大环内酯类药物最低抑菌浓度（MIC）的影响。方法在pH7．0、7.3、7．6、7．9条件下,采用微量肉汤稀释法检测红霉素、阿奇霉素、交沙霉素、克拉霉素对40株Mp的MIC,并统计分析。结果在同一pH值条件下,克拉霉索抗Mp活性最强;其次是阿奇霉素和交沙霉素;红霉素最差,且Mp对红霉素的耐药率大于12．5％（5／40）。当pH值由7．0升到7．9时,4种大环内酯类药物的MIC都逐渐降低fP〈0．05）。MIC50：红霉素降低8倍,克拉霉素16倍,阿奇霉素31倍,交沙霉素8倍;MIC90：红霉素降低至少4倍,克拉霉素16倍,阿奇霉素16倍。交沙霉素8倍。结论同一pH值条件下。抗Mp活性由强至弱排列依次为克拉霉素、阿奇霉素、交沙霉素和红霉素。Mp对红霉素存在一定程度的耐药现象。4种大环内酯类的MIC随培养基pH值升高而显著降低,即在一定pH值范围内,大环内酯类药物的抗菌活性随着pH的升高而增强。     

不同pH值对大环内酯类药物抗肺炎支原体活性的影响

目的 研究肺炎支原体(Mp)对大环内酯类药物的敏感性和耐药性以及不同pH值对大环内酯类药物最低抑菌浓度(MIC)的影响.方法 在pH 7.0、7.3、7.6、7.9条件下.采用微量肉汤稀释法检测红霉素、阿奇霉素、交沙霉素、克拉霉索对40株Mp的MIC,并统计分析.结果 在同-pH值条件下,克拉霉素抗Mp活性最强;其次是阿奇霉素和交沙霉素;红霉素最差,且Mp对红霉素的耐药率大于12.5%(5/40).当pH值由7.0升到7.9时,4种大环内酯类药物的MIC都逐渐降低(p<0.05).MIC50:红霉素降低8倍,克拉霉素16倍.阿奇霉素31倍,交沙霉索8倍:MIC90:红霉素降低至少4倍.克拉霉索16倍,阿奇霉素16倍,交沙霉素8倍.结论 同-pH值条件下,抗Mp活性由强至弱排列依次为克拉霉素、阿奇霉素、交沙霉素和红霉素.Mp对红霉素存在一定程度的耐药现象.4种大环内酯类的MIC随培养基pH值升高而显著降低,即在一定pH值范围内,大环内酯类药物的抗菌活性随着pH的升高而增强.     

大环内酯类抗菌药物在支气管扩张症中的应用

<正>支气管扩张症是一种气道慢性炎症,可因各种原因所引起,病理特征是支气管树的病理性、永久性扩张,临床特点为支气管-肺部的化脓性感染,即反复咳嗽、咳脓样痰,或伴有咯血~([1]),其特征为慢性细菌感染、肺部症状反复加重,以及中性粒细胞引起的气道炎症。支气管扩张症主要是由感染引起的,因为广泛的抗菌药物治疗和疫苗的使用,其患病率已逐渐下降。     

大环内酯类抗菌药物治疗慢性气道炎性疾病的研究进展

慢性气道炎性疾病为呼吸系统不适的常见原因,不仅导致患者生活质量严重下降,也给其家庭和社会带来巨大的经济负担。大环内酯类抗菌药物具有较强的抗菌效应,在慢性气道炎性疾病患者中的应用极为广泛。现就大环内酯类抗菌药物治疗慢性气道炎性疾病的作用机制及预后影响做一综述。     

肺炎链球菌对抗菌药物的耐药性调查及对大环内酯类抗生素耐药机制研究

目的：调查成都地区肺炎链球菌对抗菌药物的敏感性，研究成都地区肺炎链球菌对大环内酯类抗生素耐药机制。方法：收集2001年9月-2002年9月成都地区临床分离的肺炎链球菌，测定其对13种抗菌药物的耐药性及对大环内酯类抗生素的耐药表型；用聚合酶链反应(PCR)扩增耐药基因ermB和mefA，并对ermB和mefA进行基因序列分析。结果：82株肺炎链球菌中13株对青霉素低度耐药(占15．9％),肺炎链球菌对大环内酯类抗生素和克林霉素表现出较高的耐药率，对红霉素和克林霉素耐药率分别为80．5％(66／82)和68．3％(56／82)。耐大环内酯类肺炎链球菌中,96．4％菌株表现为内在型耐药。标准菌株ATCC49619及16株红霉素敏感菌株均未检测到ermB基因及mefA基因；ermB基因和；mefA基因分别在62和11株耐红霉素肺炎链球菌中检测到，其中7株菌同时检测到ermB基因和mefA基因。所测ermB和mefA基因序列与基因库收录序列高度一致。结论：成都地区临床分离的肺炎链球菌对青霉素耐药率较低，但对大环内酯类抗生素和克林霉素耐药却非常普遍。ermB基因介导的靶位改变是成都地区肺炎链球菌对大环内酯类抗生素的主要耐药机制。     

大环内酯类的药物的相互作用

近年来由于大环内酯类药物的发展，造成它们与其它药物之间潜在的药物相互作用日益增加，使其在接受联合治疗患者中的使用受到限制。因此，大环内酯类与其它药物的干扰是个值得临床重视的问题。现就其相互作用机制及临床表现作一综合介绍，以期有助于临床医生合理用药。     

空肠弯曲杆菌对大环内酯类抗菌药物耐药机制的研究进展

空肠弯曲杆菌是全球食源性急性细菌胃肠炎的主要致病因素之一,比沙门菌、志贺菌、大肠埃希菌O157：H7引发的感染更为频繁。虽然该菌引发疾病的病死率低,但其感染后遗症则较为严重,如格林-巴利综合征、瑞特综合征、反应性关节炎、肠易激综合征等。     

18种抗菌药物对厌氧菌的体外抗菌活性

近年来,头孢菌素及氟喹诺酮类抗菌药物领域的研究非常活跃,已合成许多高效、广谱、耐β-内酰胺酶的新的头孢菌素及新的氟喹诺酮类抗菌药物。本实验测定一些新型头孢菌素及氟喹诺酮类抗菌药物对临床分离的脆弱类杆菌及其他较常见的厌     

四种国产大环内酯类抗菌药物体外抗沙眼衣原体和肺炎衣原体敏感性研究

目的 研究国产必特螺旋霉素、乙酰螺旋霉素、红霉素和阿奇霉素等4种大环内酯类药物对于沙眼衣原体和肺炎衣原体体外药物敏感性试验,评估其抗衣原体作用,以指导临床用药.方法 细胞培养和免疫荧光包涵体染色技术测定4种国产大环内酯类抗菌药物对于沙眼衣原体和肺炎衣原体体外MIC.结果 对于沙眼血清型B,必特螺旋霉素、红霉素和阿奇霉素体外MIC为0.5μg/ml,乙酰螺旋霉素为4μg/ml.对于沙眼血清型D,必特螺旋霉素与阿奇霉素体外MIC均为0.25μg/ml,红霉素0.5μg/ml,乙酰螺旋霉素2μg/ml.对于肺炎衣原体,红霉素体外MIC≤0.016μg/ml,阿奇霉素和必特螺旋霉素均为0.032μg/ml,乙酰螺旋霉素0.5μg/ml.结论 国产必特螺旋霉素、红霉素和阿奇霉素体外抗沙眼衣原体(血清型B和D)和肺炎衣原体作用可靠,但乙酰螺旋霉素则较差.     

非伤寒沙门菌对喹诺酮类及头孢菌素类抗菌药物的耐药性研究

<正>1前言近年来,发达国家的非伤寒沙门菌感染发病率呈现明显的上升趋势,在美国由非伤寒沙门菌引起的食源性疾病每年约有1 400万例,而全球非伤寒沙门菌感染病例每年约有13亿例次~([1])。非伤寒沙门菌不仅是引发食源性疾病的主要病原体,也是造成非洲地区侵袭性血流感染的主要原因。据统计,非洲地区5岁以下儿童非伤寒沙门菌的年发病率为0.175%~0.388%~([2])。由     

Anti-inflammatory activity of macrolide antibiotics

The effect of four macrolide antibiotics (roxithromycin, clarithromycin, erythromycin, and azithromycin) on the generation of some mediators and cytokines involved in the inflammatory process has been studied both in vivo and in vitro. Rat carrageenin pleurisy was used as a model of acute inflammation, and the macrolides were administered (10, 20, and 40 mg/kg p.o.) 1 h before the carrageenin challenge. Exudate volume and leukocyte accumulation were both dose-dependently reduced by roxithromycin, clarithromycin and erythromycin in either normal or adrenalectomized animals. Furthermore, in normal rats, prostaglandin (PG)E(2), nitrate plus nitrite, and tumor necrosis factor-alpha levels in pleural exudate were significantly reduced by these macrolides. Roxithromycin appeared more effective than erythromycin and clarithromycin, whereas azithromycin only slightly affected the inflammatory reaction. None of the macrolides were able to modify leukotriene B(4) exudate levels. In vitro experiments have shown that the four macrolides (5-80 microM) reduced in a concentration-dependent manner the production of 6-keto-PGF(1alpha), NO(2)(-), tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 by lipopolysaccharide-stimulated J774 macrophages. In J774 cells, the inhibition of 6-keto-PGF(1alpha) and NO(2)(-) production by roxithromycin and erythromycin was not dependent on direct inhibition of cyclooxygenase-2 and inducible nitric oxide synthase activity because it appears to be related to the inhibition of cyclooxygenase-2 and inducible nitric oxide synthase protein expression. In conclusion, the present study shows that macrolide antibiotics have anti-inflammatory activity, which likely depends on their ability to prevent the production of proinflammatory mediators and cytokines, and suggest that these agents, particularly roxithromycin, can exert therapeutic effects independently of their antibacterial activity.     

Mechanisms of bacterial resistance to macrolide antibiotics

Macrolides have been used in the treatment of infectious diseases since the late 1950s. Since that time, a finding of antagonistic action between erythromycin and spiramycin in clinical isolates¹ led to evidence of the biochemical mechanism and to the current understanding of inducible or constitutive resistance to macrolides mediated by erm genes containing, respectively, the functional regulation mechanism or constitutively mutated regulatory region. These resistant mechanisms to macrolides are recognized in clinically isolated bacteria. (1) A methylase encoded by the erm gene can transform an adenine residue at 2058 (Escherichia coli equivalent) position of 23S rRNA into an ⁶ N, ⁶ N-dimethyladenine. Position 2058 is known to reside either in peptidyltransferase or in the vicinity of the enzyme region of domain V. Dimethylation renders the ribosome resistant to macrolides (MLS). Moreover, another finding adduced as evidence is that a mutation in the domain plays an important role in MLS resistance: one of several mutations (transition and transversion) such as A2058G, A2058C or U, and A2059G, is usually associated with MLS resistance in a few genera of bacteria. (2) M (macrolide antibiotics)- and MS (macrolide and streptogramin type B antibiotics)- or PMS (partial macrolide and streptogramin type B antibiotics)-phenotype resistant bacteria cause decreased accumulation of macrolides, occasionally including streptogramin type B antibiotics. The decreased accumulation, probably via enhanced efflux, is usually inferred from two findings: (i) the extent of the accumulated drug in a resistant cell increases as much as that in a susceptible cell in the presence of an uncoupling agent such as carbonylcyanide-m-chlorophenylhydrazone (CCCP), 2,4-dinitrophenol (DNP), and arsenate; (ii) transporter proteins, in M-type resistants, have mutual similarity to the 12-transmembrane domain present in efflux protein driven by proton-motive force, and in MS- or PMS-type resistants, transporter proteins have mutual homology to one or two ATP-binding segments in efflux protein driven by ATP. (3) Two major macrolide mechanisms based on antibiotic inactivation are dealt with here: degradation due to hydrolysis of the macrolide lactone ring by an esterase encoded by the ere gene; and modification due to macrolide phosphorylation and lincosamide nucleotidylation mediated by the mph and lin genes, respectively. But enzymatic mechanisms that hydrolyze or modify macrolide and lincosamide antibiotics appear to be relatively rare in clinically isolated bacteria at present. (4) Important developments in macrolide antibiotics are briefly featured. On the basis of information obtained from extensive references and studies of resistance mechanisms to macrolide antibiotics, the mode of action of the drugs, as effectors, and a hypothetical explanation of the regulation of the mechanism with regard to induction of macrolide resistance are discussed. Received: February 15, 1999 / Accepted: February 25, 1999     

Effect of drug concentration on emergence of macrolide resistance in Mycobacterium avium

The emergence of antibiotic resistance in mycobacteria involves the selection of mutant variants within a susceptible bacterial population. However, it is unclear whether antimycobacterial drugs act just as selective agents or can influence the rate of appearance of resistant mutants. The present study was initiated to address this issue by monitoring the effects of antimicrobial agents on the appearance and growth of clarithromycin (CLR)-resistant (CLR(r)) bacilli in broth cultures of Mycobacterium avium. Preexposure of M. avium to CLR had a significant dose effect on the emergence of resistance, with concentrations of 4 to 8 microg/ml resulting in a maximal (approximately 10(4)-fold) increase in the number of CLR(r) bacilli after a 4-day incubation. In addition, a dose effect was found with azithromycin. The use of combinations of CLR with either ethambutol (EMB) or rifabutin (RFB) resulted in fewer resistant bacilli compared to the use of CLR alone. The lowest active concentration of EMB (4 microg/ml) was equivalent to the EMB MIC (4 to 8 microg/ml) for the parental CLR(s) strain and the emergent CLR(r) variants, and thus, the antiresistance effect was probably the result of the bacteriostatic effect of EMB on CLR(r) bacilli. However, RFB was an order of magnitude more active (0.05 microg/ml) at reducing resistance than suggested by the MIC of this agent (0.5 to 1 microg/ml). These results indicate that the emergence of resistance was not simply the selection of a preexisting subpopulation of resistant bacilli. Further analysis suggested that early events in the emergence of resistance involved organisms (progenitors) that acquired a resistance phenotype. In addition, the progenitors appeared to be in a transient state, able to develop into a stable resistant lineage in the presence of CLR, or able to revert to the wild type in nonselective conditions.     

Potentiation of antiviral activity of acyclovir by polyene macrolide antibiotics.

The potentiation of the antiviral activity of acyclovir [9-[(2-hydroxyethoxy)methyl]guanine] by polyene macrolide antibiotics has been studied as a function of the macrolide structure. The 12 polyenes chosen for this study represented the major structural groups of these antibiotics and induced in mammalian cells repairable membrane alterations or irreversible cell damage. The potentiating activity of the polyene macrolides was determined based on the differential decrease of in vitro production of infectious virions in the presence of acyclovir alone or in combination with the polyene. Pseudorabies virus, a representative herpesvirus susceptible to acyclovir, was replicated in BHK-21 cells grown in serum-free medium to avoid the interference of serum factors in the polyene macrolide-cell interaction. The potentiation activity of the polyene antibiotics was concentration dependent. The enhancement of the antiviral activity of acyclovir was observed at polyene concentrations which had no direct effect on pseudorabies virus replication in BHK-21 cells. The optimal potentiating concentrations of polyenes were 2 to 15 times lower than that inducing 50% of potassium efflux from BHK-21 cells. The highest potentiating activity was observed for the methyl ester of the trimethylammonium derivative of aureofacin B, which reduced the pseudorabies virus titer by two orders of magnitude. Potentiation by polyene macrolides appeared to coincide with the K+-dependent membrane repair process. The acyclovir potentiating activity was associated with polyene macrolide antibiotics having a large and rigid macrolide ring (amphotericin B and aureofacin). Polyene antibiotics with small and rigid (pimaricin and filipin) or large but flexible (nystatin A1 and lienomycin) macrolide rings showed no potentiation of the antiviral effect of acyclovir.     

Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut

For clarification of the nature of the side effects of macrolide antibiotics on the gastrointestinal tract, the motor-stimulating activity of these agents was studied in unanesthetized dogs. The results showed that erythromycin and oleandomycin, the 14-membered macrolides with two side chain sugars combined at C3 and C5 in a glycosidic linkage in parallel, strongly stimulate gastrointestinal motor activity, an action accompanied by vomiting at large doses. On the other hand, leucomycin, acetylspiramycin, and tylosin, belonging to a 16-membered macrolide with two side chain sugars in series combined at C5 of the lactone ring, did not induce contractions of the gastrointestinal tract. Motor-stimulating activity by erythromycin and oleandomycin was greatly inhibited by atropine sulfate. These results point to structure-physiological activity relationships.