氟罗沙星与洛美沙星的抗生素后效应对比研究

目的:对比研究两种新氟喹诺酮药物氟罗沙星和洛美沙星的抗生素后效应。方法:应用AVANTAGE自动微生物分析仪的光密度法测定抗生素后效应。结果:氟罗沙星和洛美沙星对G 球菌和G-杆菌均产生明显的后效应,并随抗菌药物浓度的增大,对受试菌的后效应显著延长,呈现明显的浓度依赖性;经t检验,氟罗沙星对金葡菌和大肠杆菌、绿脓杆菌的后效应较洛美沙星长。结论:氟罗沙星和洛美沙星均可产生明显的后效应,提示设计给药方案时均应考虑抗生素后效应的因素。     

氟罗沙星与洛美沙星后效应的对比研究

目的研究氟喹诺酮类抗生素药物安全性,对比氟罗沙星与洛美沙星的后效应差异。方法通过光密度法对两者抑制革兰氏阴性、阳性菌产生的后效应进行测量。结果随着氟罗沙星与洛美沙星的浓度逐渐增加,PAE逐渐提升,与浓度成正比,不同浓度间比较,差异有统计学意义（P〈0.05）,4、8倍MIC时,PAE值明显高于其他浓度;同种浓度中,氟罗沙星对细菌的PAE值均高于洛美沙星（P〈0.05）。结论氟罗沙星和洛美沙星后效应作用明显,并且前者后效应长于后者,应以此为依据设计给药方案。     

阿莫西林和庆大霉素或奈替米星联合应用PAE的比较

目的 阿莫西林（AMPC）与庆大霉素（GM）或奈替米星（NTL）联合应用抗生素后效应（PAE）的比较。方法 应用光密度法测定PAE。结果 AMPC单用时对金黄色葡萄球菌和粪肠球菌有较长的PAE，对大肠埃希氏菌PAE甚小；GM和NTL单用对G^ 球菌的PAE亦很明显，对大肠埃希氏菌PAE稍短，但比单用AMPC要长。NTL的PAE比GM长，可能与受试菌对NTL敏感性高于GM有关。三种药物PAE均有随药物浓度增加而延长的趋势。AMPC与4倍MIC的GM或NTL联用时对受试菌的PAE均呈协同或相加效应；对G^ 球菌的联合PAE比G^-杆菌明显延长；AMPC与NTL的联合PAE长于与GM联合的PAE。结论 AMPC与GM或NTL联用时延长给药间隔，仍可维持强大的抗菌活性，减轻不良反应，AMPC与NTL联用优于与GM联用。     

3种青霉素类药物体外抗生素后效应

目的 比较氯唑西林（CXL），阿莫西林（AM）和美洛西林（MZL）的抗生素后效应。方法 采用AVANTAGE全自动微生物分析仪，用光密度法测定CXL、AM、MZL三种青霉素类抗生素对4种共20株临床常见致病菌的体外抗生素后效应（PAE）。结果与结论 不同品种、不同浓度的药物对不同受试菌所产生的PAE不同，对金黄色葡萄球菌、粪肠球菌有较明显的PAE，对大肠杆菌、绿脓杆菌PAE较小甚至没有。从而提示：在应用青霉素类抗生素治疗细菌感染时，除根据抗生素对细菌的MIC值外，还应考虑抗生素对细菌的PAE值。在治疗革兰氏阳性球菌所致感染时，由于PAE较长可快速静滴给药并适当延长给药间隔时间，在治疗革兰氏阴性杆菌所致感染时，由于PAE较短或没有，可主要参考药代动力学等其它因素设计给药方案。     

氨基糖甙类抗生素的体外抗生素后效应研究

目的 观察氨基糖甙类抗生素庆大霉素(GN)、奈替米星(NTL)和阿米卡星(AMK)的体外抗生素后效应(PAE).方法 应用AVANTAG全能自动化微生物分析仪用光密度测定法测定GN、NTL和AMK对4种共20株受试菌的PAE.结果 3种氨基糖甙类抗生素对受试革兰氏阳性球菌和革兰氏阴性杆菌均产生明显的PAE,亚抑菌浓度(1/2MIC)时也存在PAE,PAE值随药物浓度的增加而增大(P<0.05),表现出强的浓度依赖性,不同菌株产生不同的PAE.结论 PAE的存在提示设计氨基糖甙类抗生素给药方案时可减少给药次数,延长用药间歇,维持药物疗效,从而减轻毒副作用.     

氨基糖甙类抗生素的体外抗生素后效应研究

目的 观察氩基糖甙类抗生素庆大霉素(GN)、奈替米星(NTL)和阿米卡星(AMK)的体外抗生素后效应(PAE)。方法 应用AVANTAG全能自动化微生物分析仪用光密度测定法测定GN、NTL和AMK对4种共20株受试菌的PAE。结果 3种氩基糖甙类抗生素对受试革兰氏阳性碡菌和革兰氏阴性杆菌均产生明显的PAE，亚抑菌浓度(1／2MIC）时也存在PAE，PAE值随药物浓度的增加而增大(P<0．05)，表现出强的浓度依赖性，不同菌株产生不同的PAE。结论 PAE的存在提示设计氯基糖甙类抗生素给药方案时可减少给药次数，延长用药间歇，维持药物疗效，从而减轻毒副作用。     

国产氟罗沙星体外抗菌活性研究

测定国产氟罗沙星对４９３株临床分离细菌的最低抑菌浓度（ＭＩＣ），并与氧氟沙星、洛美沙星、环丙沙星和几种头孢菌素、氨基糖苷类抗生素作了比较。结果表明：氟罗沙星对革兰氏阴性细菌有强大抗菌活性，对肠杆菌科细菌的ＭＩＣ９０≤１μｇ／ｍｌ。对铜绿假单胞菌亦有较强抗菌活性，其ＭＩＣ５０、ＭＩＣ９０分别为２和４μｇ／ｍｌ。金葡球菌（含ＭＲＳＡ菌株）对氟罗沙星亦很敏感，ＭＩＣ９０≤１μｇ／ｍｌ。链球菌属对其基本耐药，ＭＩＣ９０为８～１６μｇ／ｍｌ。对大多数常见致病菌，氟罗沙星体外抗菌活性与氧氟沙星、洛美沙星相近，稍逊于环丙沙星。对革兰氏阴性菌，氟罗沙星与头孢噻肟、头孢他啶、阿米卡星相当，优于头孢唑林、氨苄西林、哌拉西林、庆大霉素。耐庆大霉素、头孢菌素菌株对氟罗沙星仍敏感。细菌对氟罗沙星单步自发耐药突变频率极低，但通过连续传代培养可以培育出对氟罗沙星高度耐药菌株。     

抗产超广谱β-内酰胺酶菌属药物的后效应

目的：测定5种抗菌药物对产超广谱β-内酰胺酶菌属(ESBLs)的抗菌药物后效应(PAE)。方法：ESBLs菌属分离鉴定采用SCAN4全自动细菌分析仪；MIC测定应用微量肉汤稀释法；PAE采用光密度法。结果：碳青霉烯类、氨基糖苷类和氟喹诺酮类对产ESBLs菌的PAE都比较长，并且随药物浓度的增加，PAE均有增加的趋势，在16倍MIC时PAE有明显延长。结论：碳青霉烯类、氨基糖苷类和氟喹诺酮类对产ESBLs菌的PAE都较明显，在设计给药方案时应重视PAE的影响，适当增加药物单剂量和延长给药间隔时间。     

司帕沙星对小鼠肾脏感染的有效性

司帕沙星(Sparfloxacin)是一种喹诺酮类新药,对革兰氏阳性菌,如葡萄球菌、链球菌和肠球菌具有广谱,强效的抗菌活性。特别是对革兰氏阴性菌,如肠道细菌、假单孢菌属和流感嗜血菌,以及各种枝原体、军团菌、衣原体和分枝杆菌均显示强大的抗菌作用。司帕沙星对革兰氏阳性菌的抗菌活性超过环丙沙星或氟罗沙星,并且它对肠道细苗族和非发酵菌的抗菌活性与环丙沙星和氟罗沙星一样有效。小白鼠肾脏溃疡模型实验证实了司帕沙星的有效性,并与氟罗沙星作了对比。     

护康-氟罗沙星葡萄糖注射液121例不良反应分析

护康-氟罗沙星葡萄糖注射液，为第三代氟喹诺酮类之氟罗沙星0．2g与葡萄糖5．0g制备的100ml输液制剂，具有抗菌范围广、抗菌作用强、吸收迅速、组织内和细胞内药物浓度高、血浆半衰期较长的特点。使用时，每日仅需给药1次。现临床广泛应用于治疗呼吸、泌尿、生殖、消化等系统的感染，及皮肤     

氧氟沙星与哌拉西林单用或联合应用的抗生素后效应

本文应用ＡＶＡＮＴＡＧＥ分析仪的微生物比浊法测定了氧氟沙星（ＯＦＬＸ）与哌拉西林（ＰＩＰＣ）单用或联合应用的抗生素后效应（ＰＡＥ），结果表明ＯＦＬＸ单用时对受试革兰氏阳性球菌和革兰氏阴性杆菌均产生明显的ＰＡＥ；ＰＩＰＣ单用时对革兰氏阳性球菌ＰＡＥ较明显，对革兰氏阴性杆菌ＰＡＥ较小，两药单用时ＰＡＥ值随药物浓度增高而显著增大，而两药联用时，对革兰氏阴性杆菌均呈现协同或相加ＰＡＥ；对革兰氏阳球菌的ＰＡ     

舒巴克坦对头孢哌酮体外抗生素后效应的影响

目的 考察合用β-内酰胺酶抑制剂舒巴克坦（ＳＢＴ）前后头孢哌酮（ＣＰＺ）对４种致病菌抗生素后效应（ＰＡＥ）的变化。方法 采用特异性β-内酰胺酶鉴定试剂Ｎｉｔｒｏｃｅｆｉｎ挑选大肠埃希氏杆菌、金黄色葡萄球菌、变形杆菌和绿脓假单胞菌的产酶菌株，用比浊法测定受试菌株在不同ＣＰＺ浓度时的ＰＡＥ值。结果 合用ＳＢＴ后，ＣＰＺ对产酶菌株的ＰＡＥ均有不同程度的延长，低浓度时（１／２，１倍ＭＩＣ）ＰＡＥ增加更明显（Ｐ＜０．０５）。结论 合并ＣＰＺ和ＳＢＴ的给药方案对治疗产β-内酰胺酶菌株引起的感染有利，尤其在体内药物浓度较低时，合并用药可以更长时间地抑制细菌生长。     

3种青霉素类药物体外抗生素后效应

目的 比较氯唑西林（ＣＸＬ），阿莫西林（ＡＭ）和美洛西林（ＭＺＬ）的抗生素后效应。方法 采用ＡＶＡＮＴＡＧＥ全自动微生物分析仪，用光密度法测定ＣＸＬ、ＡＭ、ＭＺＬ三种青霉素类抗生素对 ４种共２０株临床常见致病菌的体外抗生素后效应（ＰＡＥ）。结果与结论 不同品种、不同浓度的药物对不同受试菌所产生的ＰＡＥ不同，对金黄色葡萄球菌、粪肠球菌有较明显的ＰＡＥ，对大肠杆菌、绿脓杆菌ＰＡＥ较小甚至没有。从而提示：在应用青霉素类抗生素治疗细菌感染时，除根据抗生素对细菌的ＭＩＣ值外，还应考虑抗生素对细菌的ＰＡＥ值。在治疗革兰氏阳性球菌所致感染时，由于ＰＡＥ较长可快速静滴给药并适当延长给药间隔时间，在治疗革兰氏阴性杆菌所致感染时，由于ＰＡＥ较短或没有，可主要参考药代动力学等其它因素设计给药方案。     

Postantibiotic effects and postantibiotic sub-MIC effects of erythromycin, roxithromycin, tilmicosin, and tylosin on Pasteurella multocida

When intermittent dosing is used during treatment, the concentrations of antibiotics fluctuate and subinhibitory concentrations may occur between doses. Postantibiotic effects (PAEs) and postantibiotic subinhibitory effects (PA SMEs) on bacteria may provide additional, valuable information for the rational use of a drug in clinical practice. In this study tilmicosin was the most active antibiotic tested against P. multocida type D with MICs ranging from 4–16 mg/l. Roxithromycin and tilmicosin induced a statistically significantly longer PAE than did tylosin against P. multocida types A and D (P<0.05). The duration of PAEs and PA SMEs were proportional to the concentrations of drugs used for exposure. The PA SMEs were substantially longer than PAEs on P. multocida. Tilmicosin had a longer PA SME compared with erythromycin, roxithromycin and tylosin for P. multocida. The computerized incubator used in the present study provided an efficient and convenient determination of PAE and PA SME, allowing frequent measurements of the bacterial growth.     

Postantibiotic effects and postantibiotic sub-MIC effects of erythromycin, roxithromycin, tilmicosin, and tylosin on Pasteurella multocida

When intermittent dosing is used during treatment, the concentrations of antibiotics fluctuate and subinhibitory concentrations may occur between doses. Postantibiotic effects (PAEs) and postantibiotic subinhibitory effects (PA SMEs) on bacteria may provide additional, valuable information for the rational use of a drug in clinical practice. In this study tilmicosin was the most active antibiotic tested against P. multocida type D with MICs ranging from 4–16 mg/l. Roxithromycin and tilmicosin induced a statistically significantly longer PAE than did tylosin against P. multocida types A and D (P<0.05). The duration of PAEs and PA SMEs were proportional to the concentrations of drugs used for exposure. The PA SMEs were substantially longer than PAEs on P. multocida. Tilmicosin had a longer PA SME compared with erythromycin, roxithromycin and tylosin for P. multocida. The computerized incubator used in the present study provided an efficient and convenient determination of PAE and PA SME, allowing frequent measurements of the bacterial growth.     

Postantibiotic and physiological effects of tilmicosin, tylosin, and apramycin at subminimal and suprainhibitory concentrations on some swine and bovine respiratory tract pathogens.

The antimicrobial activity of tilmicosin, tylosin, and apramycin on some important gram-negative swine and bovine pathogens namely, Pasteurella multocida, Pasteurella haemolytica, Bordetella bronchiseptica, and Actinobacillus pleuropneumoniae were studied in vitro. The effect of minimal inhibitory concentrations (MICs) and sub-MICs (1/4, 1/2 MIC) on bacterial growth was evaluated. The presence of tilmicosin, tylosin and apramycin in the medium decreased the rate of growth of the bacterial strains tested using drug concentrations as low as 1/4 MIC. The postantibiotic effect (PAE) which is the suppression of optimal bacterial growth that persists after a short exposure (2 h) of microorganisms to an antibiotic was studied by exposure of bacteria to drugs at 1/4, 1/2, 1, 4 and 8 times MIC. The duration of PAEs increased with rising concentration for all drugs tested but at concentrations below the MIC, tilmicosin showed more significant PAEs than tylosin or apramycin against P. multocida and A. pleuropneumoniae. Tilmicosin and tylosin caused PAEs of up to 8 h when used at 8 times the MIC, while apramycin caused PAEs of up to 5 h when used at this concentration. Sub-MICs of either tilmicosin, tylosin, or apramycin had no effect on P. multocida dermonecrotic toxin production. However sub-MICs of tylosin, or apramycin significantly reduced the haemolytic activity of A. pleuropneumoniae and affected the capsular material production of this isolate and of one isolate of P. multocida (type A). The in vitro effect of tilmicosin, tylosin, and apramycin (even when used at sub-MIC levels) on growth, production of capsular material, and haemolytic activity might impair the virulence of some of the microorganisms studied. In addition to the effects of these drugs on some putative virulence factors, we suggest that the strong PAEs caused by tilmicosin, tylosin, and apramycin may also contribute to the in vivo efficacy of these drugs.     

Anticonvulsant profile of drugs which facilitate GABAergic transmission on convulsions mediated by a GABAergic mechanism

The effects of selected modulators of GABAergic transmission, either alone or in combination, were tested for their potency on the seizure pattern and mortality induced by convulsant drugs in rat. Pentobarbital and diazepam were effective against both tonic and clonic seizure components induced by bicuculline and picrotoxin. The anticonvulsant profile of ethanol closely resembled that of pentobarbital. Pentobarbital, diazepam and ethanol did not modify seizures induced by strychnine. In contrast, progabide, a central gamma-aminobutyric acid (GABA) receptor agonist, caused significant protection only against convulsions induced by strychnine and its lethality, but did not protect against seizures induced by bicuculline or picrotoxin. Data on interaction of drugs with subprotective doses of these agents clearly demonstrated potentiation of the anticonvulsant actions of these modulators. Thus, seizures induced by bicuculline were more sensitive to the inhibition by pentobarbital in combination with diazepam or ethanol, while pentobarbital with progabide was equally effective against convulsions induced by GABA antagonists. Diazepam, in combination with progabide, blocked only convulsions induced by picrotoxin. Ethanol, in combination with either pentobarbital or with diazepam, was effective against all the three convulsant drugs. These results are consistent with the concept that drugs which facilitate GABAergic transmission are effective against seizures related to an impairment of GABA transmission. Further, the present data indicate that tonic seizures are more susceptible to the actions of drugs than the clonic component. Smaller doses of these drugs, alone or in combination, modified the seizure patterns and mortality, whereas at larger doses, the possible involvement of a nonspecific depressant action cannot be ruled out.     

Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis

Purpose

Analog development of existing drugs and direct drug delivery to the lungs by inhalation as treatments for multiple and extensively drug resistant (MDR and XDR) tuberculosis (TB) represent new therapeutic strategies. Pyrazinamide (PZA) is critical to drug sensitive TB therapy and is included in regimens for MDR TB. However, PZA-resistant Mycobacterium tuberculosis (Mtb) strains threaten its use. Pyrazinoic acid esters (PAEs) are PZA analogs effective against Mtb in vitro, including against the most common PZA resistant strains. However, PAEs require testing for TB efficacy in animal models.

Methods

PAEs were delivered daily as aqueous dispersions from a vibrating mesh nebulizer to Mtb infected guinea pigs for 4 weeks in a regimen including orally administered first-line TB drugs.

Results

PAEs tested as a supplement to oral therapy significantly reduced the organ bacterial burden in comparison to infected, untreated control animals. Thus, PAE aerosol therapy is a potentially significant addition to the regimen for PZA resistant MDR-TB and XDR-TB treatment. Interestingly, low dose oral PZA treatment combined with standard therapy also reduced bacterial burden. This observation may be important for PZA susceptible disease treatment.

Conclusion

The present study justifies further evaluation of PZA analogs and their lung delivery to treat TB.

     

Postantibiotic effect of purified melittin from honeybee (Apis mellifera) venom against Escherichia coli and Staphylococcus aureus

Since the ancient times, the antibacterial application of honeybee venom (BV) has been practised and persisted. We investigated the antibacterial activity of whole BV and purified melittin against Escherichia coli and Staphylococcus aureus by the minimum inhibitory concentrations (MICs) and the postantibiotic effects (PAEs). The in vitro PAEs of whole BV and isolated melittin were determined using E. coli and S. aureus. The PAEs of whole BV against E. coli and S. aureus were 0.15 h (1 × MIC), 2.4 h (5 × MIC), and 3.45 h (1 × MIC), respectively. The PAEs of melittin against E. coli and S. aureus were 0.1 h (1 × MIC), 3.2 h (5 × MIC), and 4.35 h (1 × MIC), respectively. These results suggest that whole BV and melittin will be developed as a novel antibacterial drug.