山楂果胶寡糖联用氟喹诺酮类药物对葡萄球菌防耐药浓度的影响分析

目的 探讨山楂果胶寡糖与氟喹诺酮联合用药对金黄色葡萄球菌防耐药浓度的影响,为临床合理使用现有抗生素、防治细菌耐药产生提供理论依据.方法 采用标准琼脂二倍稀释法测定左氧氟沙星、环丙沙星对30株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度(MIC),采用标准琼脂平板稀释法测定2种FQ药物对临床分离金黄色葡萄球菌的防突变浓度,计算单药和联合山楂果胶寡糖用药后该药的MPC50、MPC90.结果 左氧氟沙星单药对30株金黄色葡萄球菌的MPC范围在2～64mg/L,MPC90为32mg/L;联合山楂果胶寡糖后MPC范围为0.5～16 mg/L,MPC90降至8 mg/L.环丙沙星单药对30株金黄色葡萄球菌的MPC范围1～32mg/L,MPC90为16mg/L;联合山楂果胶寡糖后MPC范围0.25～8mg/L,MPC90降至4 mg/L,两组各项指标比较差异有显著性(P<0.05).结论 联合山楂果胶寡糖用药能降低环丙沙星、左氧氟沙星MPC,减少细菌耐药突变体的选择性富集扩增,防止抗菌药物耐药的产生.     

山楂果胶寡糖联用氟喹诺酮类药物对葡萄球菌防耐药浓度的影响分析

目的 探讨山楂果胶寡糖与氟喹诺酮联合用药对金黄色葡萄球菌防耐药浓度的影响,为临床合理使用现有抗生素、防治细菌耐药产生提供理论依据.方法 采用标准琼脂二倍稀释法测定左氧氟沙星、环丙沙星对30株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度(MIC),采用标准琼脂平板稀释法测定2种FQ药物对临床分离金黄色葡萄球菌的防突变浓度,计算单药和联合山楂果胶寡糖用药后该药的MPC50、MPC90.结果 左氧氟沙星单药对30株金黄色葡萄球菌的MPC范围在2～64mg/L,MPC90为32mg/L;联合山楂果胶寡糖后MPC范围为0.5～16 mg/L,MPC90降至8 mg/L.环丙沙星单药对30株金黄色葡萄球菌的MPC范围1～32mg/L,MPC90为16mg/L;联合山楂果胶寡糖后MPC范围0.25～8mg/L,MPC90降至4 mg/L,两组各项指标比较差异有显著性(P<0.05).结论 联合山楂果胶寡糖用药能降低环丙沙星、左氧氟沙星MPC,减少细菌耐药突变体的选择性富集扩增,防止抗菌药物耐药的产生.     

山楂果胶寡糖联用氟喹诺酮类药物对葡萄球菌防耐药浓度的影响分析

目的探讨山楂果胶寡糖与氟喹诺酮联合用药对金黄色葡萄球菌防耐药浓度的影响,为临床合理使用现有抗生素、防治细菌耐药产生提供理论依据。方法采用标准琼脂二倍稀释法测定左氧氟沙星、环丙沙星对30株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度（MIC）,采用标准琼脂平板稀释法测定2种FQ药物对临床分离金黄色葡萄球菌的防突变浓度,计算单药和联合山楂果胶寡糖用药后该药的MPC50、MPC90。结果左氧氟沙星单药对30株金黄色葡萄球菌的MPC范同在2～64mg／L,MPC90为32mg／L;联合山楂果胶寡糖后MPC范围为0．5～16mg／L,MPC90降至8mg／L。环丙沙星单药对30株金黄色葡萄球菌的MPC范围1～32mg／L,MPC90为16mg／L;联合山楂果胶寡糖后MPC范围0．25～8mg／L,MPC90降至4mg／L,两组各项指标比较差异有显著性伊〈0．05）。结论联合山楂果胶寡糖用药能降低环丙沙星、左氧氟沙星MPC,减少细菌耐药突变体的选择性富集扩增,防止抗菌药物耐药的产生。     

Usefulness of various antibiotics against Mycobacterium avium-intracellulare, measured by their mutant prevention concentration

This study looked the selection of resistant mutants in Mycobacterium avium-intracellulare during antibiotic treatment. The mutant prevention concentration (MPC) of 20 Mycobacterium avium and 12 Mycobacterium intracellulare isolates was determined. Fifty percent of Mycobacterium avium strains had MPC (MPC50) values lower than 16, 64, 40, 55 and 60 mg/L for rifabutin, rifampicin, ciprofloxacin, levofloxacin and moxifloxacin, respectively. In the case of Mycobacterium intracellulare, 50% had MPC (MPC50) values below 60, 30, 35, 16, 2.5 and 14 mg/L for linezolid, rifabutin, levofloxacin, gatifloxacin, moxifloxacin and clarithromycin, respectively. The high capacity for selecting resistant mutants of all the antibiotics studied emphasises the need to restore the immune system if necessary and to administer combined treatments in order to cure patients.     

In vitro activities of mutant prevention concentration-targeted concentrations of fluoroquinolones against Staphylococcus aureus in a pharmacodynamic model

To test the validity of the mutant selection window, we simulated mutant prevention concentration-targeted fluoroquinolone concentrations using an in vitro model with infected fibrin clots. Therapeutic ciprofloxacin (peak 5 microg/mL; t(1/2) 4 h), gatifloxacin (3.5 microg/mL; 8h), gemifloxacin (1.25 microg/mL; 8 h), levofloxacin (6 microg/mL; 6 h) and moxifloxacin (4.5 microg/mL; 12 h) were tested against methicillin-susceptible and -resistant Staphylococcus aureus, as were mutant prevention concentration (MPC)-targeted regimens achieving a trough of 1/4x or 2x MPC. MIC/MPC for MSSA K553 were 0.125/2, 0.03/0.125, 0.03/0.063, 0.125/1 and 0.015/0.25 microg/mL for ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin, respectively. Corresponding values for MRSA 494 were 0.125/1, 0.063/0.125, 0.03/0.063, 0.125/0.5 and 0.063/0.125 microg/mL. All regimens produced efflux mutants of MSSA K553. For MRSA 494, therapeutic and 1/4x MPC levofloxacin regimens produced resistance, whereas only 1/4x MPC regimens of gatifloxacin, gemifloxacin, and moxifloxacin produced resistance. All ciprofloxacin regimens produced resistance. Ciprofloxacin 1/4x MPC and therapeutic levofloxacin caused outgrowth of GrlA mutants (S80Y amino acid substitution); efflux mutants were isolated in all other cases. Overall, gatifloxacin, gemifloxacin, and moxifloxacin displayed a lesser propensity to select resistant isolates of S. aureus than ciprofloxacin and levofloxacin. The mutant selection window premise appeared valid for MRSA only. Additional studies are necessary to define the applicability of the MPC.     

3种氟喹诺酮类药物对鲍曼不动杆菌的防耐药突变浓度研究

目的研究3种氟喹诺酮类药物对临床分离的鲍曼不动杆菌敏感株及其环丙沙星诱导突变株的防耐药突变浓度（MPC）,比较其防耐药突变能力。方法用环丙沙星琼脂平板筛选鲍曼不动杆菌临床分离株的突变株,用琼脂平板稀释法测定各实验菌株的最低抑菌浓度（MIC）和MPC。结果加替沙星和左氧氟沙星对临床分离株及其突变株的MPC低于环丙沙星。对临床分离株的MPC,加替沙星和左氧氟沙星均为0．25μg／mL,环丙沙星为2μg／mL;对突变株的MPC,加替沙星和左氧氟沙星为1～8μg／mL,环丙沙星为4～32μg/mL。结论对临床分离的鲍曼不动杆菌敏感株及其环丙沙星诱导的突变株,加替沙星和左氧氟沙星限制其耐药突变株的选择能力强于环丙沙星;对环丙沙星敏感的鲍曼不动杆菌的临床治疗,建议要避免这3种氟喹诺酮类的单药治疗。     

Mutant prevention concentrations of garenoxacin against Streptococcus pneumoniae isolates from otorhinolaryngological infections

The minimum inhibitory concentrations (MICs) and the mutant prevention concentrations (MPCs) of garenoxacin (GRNX), were compared to those of levofloxacin (LVFX), and moxifloxacin (MFLX) against 78 Streptococcus pneumoniae isolates from otorhinolaryngological infections in Japan during the period January 2007 to June 2007. The MIC and MPC for 90% of the isolates (MIC90 and MPC90) of GRNX were 0.06 and 0.12 microg/mL, respectively, and were the lower values than LVFX and MFLX MIC90s and MPC90s. The ratios of MPC/MIC of GRNX were the lower values than those of LVFX and MFLX.     

Microbiological rationale for the utilisation of prulifloxacin, a new fluoroquinolone, in the eradication of serious infections caused by Pseudomonas aeruginosa

Minimal inhibitory concentrations (MICs) of prulifloxacin were evaluated in comparison with ciprofloxacin, levofloxacin and moxifloxacin against a large collection (N = 300) of Pseudomonas aeruginosa strains characterised according to the CLSI/NCCLS microdilution method. Additional in vitro tests (time-kill curves and mutant prevention concentration (MPC) determinations) were carried out. Assuming a susceptibility breakpoint for prulifloxacin identical to that of ciprofloxacin, the new fluoroquinolone emerged as the most potent antibiotic (72% of susceptible strains versus 65%, 61% and 23% for ciprofloxacin, levofloxacin and moxifloxacin, respectively). Time-kill tests at 4x MIC confirmed the pronounced bactericidal potency of the drug against P. aeruginosa. Amongst the members of the fluoroquinolone class assessed, prulifloxacin produced the lowest MPC values (< or = 4 mg/L). Our in vitro results indicate that prulifloxacin represents the most powerful antipseudomonal drug available today.     

氟喹诺酮类药物浓度对预防肺炎链球菌耐药的影响研究

目的检测氟喹诺酮类药物对肺炎链球菌临床耐药的预防作用,并比较防突变浓度（MPC）与最低抑菌浓度（MIC）间的关系,为临床合理用药提供依据。方法采用琼脂二倍稀释法检测5种抗菌药物的MIC值,计算MIC50和MIC90值;采用新鲜制备的1010 CFU/mL菌液测定MPC值,测定MPC值,接种细菌浓度〉1010,计算MPC50和MPC90值,并比较MPC/MIC。结果在5种药物中,莫西沙星的MPC50和MPC90值最低,分别为1mg/L和2mg/L,环丙沙星最高,为16mg/L和32mg/L;测定菌株对莫西沙星、左氧沙星的MPC/MIC范围主要在8～16,对加替沙星、司巴沙星的MPC/MIC范围主要在16～32,对环丙沙星的MPC/MIC范围主要在32～64。结论莫西沙星、左氧沙星抗菌谱广,而且MPC值较低,并可以防止肺炎链球菌突变的发生。     

2种氟喹诺酮类药物对临床分离金黄色葡萄球菌突变选择窗的影响

目的通过测定左氧氟沙星及莫西沙星对金黄色葡萄球菌临床分离菌株防突变浓度(MPC),比较氟喹诺酮类对金黄色葡萄球菌突变选择窗(MSW)的影响,为临床合理使用抗菌药物,防治细菌耐药产生提供依据。方法采用标准琼脂二倍稀释法测定2种氟喹诺酮药物对38株临床分离的金黄色葡萄球菌和金黄色葡萄球菌质控菌株ATCC25923的最低抑菌浓度(MIC),采用肉汤法富集3×1010CFU.mL-1的金黄色葡萄球菌测定2种氟喹诺酮药物MPC,计算MPC50、MPC90、MPC/MIC。结果左氧氟沙星对38株金黄色葡萄球菌的MPC90、MPC90/MIC90分别为16 mg.L-1、8,莫西沙星分别为2 mg.L-1、4;结合药物动力学参数莫西沙星400 mg.次-1,1次.d-1,其Cmax/MPC90、AUC/MPC90分别为2.3、18,左氧氟沙星500 mg.次-1的Cmax/MPC90、AUC/MPC90明显高于300 mg.d-1组,分别为0.5、2.4。结论对金黄色葡萄球菌的临床分离菌株莫西沙星比左氧氟沙星MPC90低,MSW窄,防突变能力更强。左氧氟沙星500 mg.次-1,1次.d-1,能够提高左氧氟沙星的防突变能力。     

6种氟喹诺酮类药物对凝固酶阴性葡萄球菌的防耐药变异浓度分析

目的 比较6种氟喹诺酮类药物对临床分离凝固酶阴性葡萄球菌耐药突变体的选择能力.方法 选择呼吸道标本,对苯唑西林、环丙沙星敏感的凝固酶阴性葡萄球菌34株,采用标准琼脂二倍稀释法、标准琼脂平板稀释法,测定6种氟喹诺酮类药物对凝固酶阴性葡萄球菌的最低抑菌浓度(MIC)、防耐药变异浓度(MPC).结果 MPC值比较,莫西沙星最低(MPC90为1 mg/L),左氧氟沙星和环丙沙星最高(MPC90均为32 mg/L).莫西沙星、卡屈沙星和加替沙星的MPC90/MIC90较低,均为2.结论 莫西沙星、卡屈沙星和加替沙星对凝固酶阴性葡萄球菌的MPC值较低,突变选择窗范围相对较窄.     

Comparison of minimal inhibitory and mutant prevention drug concentrations of 4 fluoroquinolones against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus

Staphylococcus aureus remains an important human pathogen affecting both outpatients and those hospitalized. Increasing antimicrobial resistance is global but prevalence rates are variable for different geographical areas. Fluoroquinolones have been used to treat S. aureus infections and the newer quinolones have enhanced in vitro activity against this organism. The mutant prevention concentration (MPC) defines the antimicrobial drug concentration threshold that would require an organism to simultaneously possess two mutations for growth in the presence of the drug. We tested clinical isolates of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus by minimum inhibitory concentration (MIC) and MPC against gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin. For MSSA strains, the rank order of potency based on MIC(90) values were gemifloxacin (0.063 mg/l) = moxifloxacin (0.063 mg/l) > gatifloxacin (0.05 mg/l) = levofloxacin (0.25 mg/l) and by MPC values moxifloxacin (0.25 mg/l) > gemifloxacin (0.5 mg/l) > gatifloxacin (1 mg/l) = levofloxacin (1mg/l). For 87% of the isolates the MPC value was 0.5 mg/l for gatifloxacin. The rank order of potency based on the time the serum drug concentration exceeded the MPC(90), was as follows: moxifloxacin (>24 h) > levofloxacin (>18 h) > gatifloxacin (12 h) > gemifloxacin (9 h). Serum drug concentration remained in excess of the MPC(87) for 24 h for gatifloxacin. Both MIC(90) and MPC(90) values were higher against MRSA strains and the time above the MPC(90) was significantly shorter for all agents.     

环丙沙星联合多西环素对金黄色葡萄球菌防耐药突变浓度的影响

目的探讨环丙沙星联用多西环素对金黄色葡萄球菌防耐药突变浓度(MPC)值的影响,为防止产生细菌耐药提供依据。方法应用肉汤法富集浓度为1010CFU/ml金黄色葡萄球菌ATCC29213菌株,采用琼脂平板二倍稀释法测定环丙沙星、多西环素单药以及2药以不同浓度联用时对金黄色葡萄球菌ATCC29213的防耐药突变浓度(MPC)和耐药突变选择窗(MSW)。结果环丙沙星、多西环素单药对金黄色葡萄球菌ATCC29213的MPC分别为3.00和20.16μg/ml,MSW分别为10和84。在联用多西环素浓度由0.12μg/ml至15.36μg/ml时,环丙沙星对ATCC29213的MPC由3.00μg/ml下降至0.30μg/ml。在联用环丙沙星浓度由0.30μg/ml至2.60μg/ml时,多西环素对ATCC29213的MPC由15.36μg/ml下降至0.24μg/ml。结论多西环素和环丙沙星联合用药可使各自单药对金黄色葡萄球菌ATCC29213的MPC下降,MSW减小。     

利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

目的：比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度（MPC）和最低抑菌浓度（MIC）的相关性。方法：采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌（MRSA）临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利夺唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果：利奈唑胺、万古霉素对35株MRSA的MPC90值（抑制90％的细菌发生细菌耐药的最低防耐药突变体选择浓度）分别为16.8μg／mL,选择指数（MPC90／MIC90）均为8。两药对MRSA的MPC和MIC的线性相关系数R^2分别为0．32和0．008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论（MSW）中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论：万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。     

比较6种氟喹诺酮类药物对金黄色葡萄球菌的防耐药变异浓度

目的比较6种氟喹诺酮类药物对临床分离金黄色葡萄球菌耐药突变体的选择能力。方法用呼吸道标本,选择对苯唑西林、环丙沙星敏感的金黄色葡萄球菌36株,采用标准琼脂二倍稀释法、标准琼脂平板稀释法,测定6种氟喹诺酮类药物对金黄色葡萄球菌的MIC、MPC。结果 MPC值比较,莫西沙星最低;而环丙沙星最高。选择指数(MPC90/MIC90)较低有如下4种:莫西沙星、卡屈沙星、加替沙星和帕珠沙星,均为2。6种药物MPC90值与其体内药动学参数比较,莫西沙星和卡屈沙星小于其Cmax。结论莫西沙星、卡屈沙星和加替沙星对金葡菌的MPC值较低,突变选择窗范围相对较窄。     

左奥硝唑等4种抗菌药的防耐药突变浓度测定及临床用药剂量合理性的分析

目的：测定左奥硝唑、亚胺培南西司他丁钠、莫西沙星和替硝唑单用或联用时的防耐药突变浓度,为临床上的合理用药提供依据。方法：选用体外脆弱拟杆菌ATCC25285,分别以微量肉汤稀释法测定供试药物的体外最低抑菌浓度;棋盘格法测定分级抑菌浓度指数;平板法测定单独用药及联合用药后的防耐药突变浓度。分析比较各药防耐药突变浓度与体内最大血药浓度之间的关系。结果：左奥硝唑、亚胺培南西司他丁钠、莫西沙星和替硝唑单独使用时对脆弱拟杆菌ATCC25285的防耐药突变浓度分别为10．24、5．12、4．0和20．24mg·L-1;按临床目前使用的常规剂量,各药的体内最大血药浓度与其防耐药突变浓度之比分别为1．82、2．73～4．69、0．75～1．0和0．684～1．02;而左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用后的防耐药突变浓度分别降低为3．2和1．6mg·L-1,联用后的FIC分别为0．75和0．5。表明左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用可明显缩小各自的防耐药突变浓度。结论：左奥硝唑在目前的常规剂量下,不易引起耐药性,但替硝唑的剂量应予适当增加。左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用有助于减少耐药性。     

Activity of moxifloxacin and other quinolones against pneumococci resistant to first-line agents, or with high-level ciprofloxacin resistance

The activity of moxifloxacin and other quinolones was assessed against 288 epidemiologically diverse isolates of Streptococcus pneumoniae, many of them resistant to one or more first-line agents and/or with increased ciprofloxacin resistance (minimum inhibitory concentrations, MICs 16- > 64 mg/l compared with 1-2 mg/l for most isolates). Moxifloxacin and grepafloxacin were the most active quinolone analogues, inhibiting about 90% of the isolates at < or = 1 mg/l, whereas levofloxacin inhibited 64% of isolates at < = 1 mg/l and ciprofloxacin inhibited 42%. Moxifloxacin also was the most active agent against isolates with elevated ciprofloxacin resistance (MIC 16- > 64 mg/l): moxifloxacin MICs of around 4 mg/l were seen for most such isolates, compared with 16-32 mg for levofloxacin and grepafloxacin. The activity of moxifloxacin against pneumococci resistant to one or more first-line agent suggests it will have a useful therapeutic role, although its activity against highly ciprofloxacin resistant isolates seems marginal.     

Concentrations in plasma, urinary excretion and bactericidal activity of levofloxacin (500 mg) versus ciprofloxacin (500 mg) in healthy volunteers receiving a single oral dose

In a randomised crossover study, 14 volunteers received a single oral dose of 500 mg levofloxacin or 500 mg ciprofloxacin in order to assess plasma concentrations by high-pressure liquid chromatography (up to 24 h), urinary excretion and urinary bactericidal titres (UBTs) at intervals up to 120 h. The median maximum concentration of levofloxacin in plasma was 6.1 mg/L and that of ciprofloxacin was 2.3 mg/L. The median cumulative level of renal excretion of the administered dose of the parent drug was 81.2% for levofloxacin and 36.2% for ciprofloxacin. UBTs were determined for a reference strain and nine clinical uropathogens. The median UBTs of both quinolones measured within the first 12 h were between 0 and 1:≥1024, correlating with the minimum inhibitory concentrations (MICs) of the strains. For Gram-negative strains, the UBTs of both quinolones were comparable despite the lower MICs of ciprofloxacin. During further time courses, however, the UBTs of levofloxacin were significantly higher than those of ciprofloxacin. For Gram-positive strains, for which the MICs of levofloxacin were equal to or lower than those of ciprofloxacin, the UBTs of levofloxacin were already significantly higher from the beginning. It can be concluded that overall the doses of the two tested fluoroquinolones may be considered equivalent with regard to treatment of complicated urinary tract infections, although the recommended dosing is twice daily for ciprofloxacin and once daily for levofloxacin.     

In vitro activity of linezolid,synercid and telithromycin against genetically defined high level fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus

The in vitro activity of levofloxacin, moxifloxacin, gatifloxacin, erythromycin, telithromycin, linezolid, synercid and vancomycin was measured against 36 genetically defined, gyrA/grlA double mutant MRSA clinical strains with an MIC to ciprofloxacin > or = 8 mg/l. The three newer fluoroquinolones tested were more active than ciprofloxacin. Resistance rates for levofloxacin and gatifloxacin were high (44.5 and 36.1%, respectively). All the strains were moxifloxacin-susceptible, though most of them had MICs close to the break point. All the strains were intermediate or resistant to erythromycin and most were also resistant to telithromycin. No strains were resistant to linezolid, synercid or vancomycin (MIC(90): 2, 1 and 2 mg/l, respectively).     

In vitro activity of four fluoroquinolones against clinical isolates of Pseudomonas aeruginosa determined by the E test

Ciprofloxacin, levofloxacin, ofloxacin, and trovafloxacin were tested by the E-test against 100 clinical isolates of Pseudomonas aeruginosa. Ciprofloxacin was the most active of the tested agents with 82% of isolates having a MIC 8). Levofloxacin and trovafloxacin had nearly identical potency: 75% and 76% of the isolates were inhibited by 8 for levofloxacin; 0.19->8 for trovafloxacin). Ofloxacin was the least active of the four quinolones, with 43% of the isolates having a MIC >2 mg/l. All isolates resistant to ciprofloxacin were also resistant to the other agents, i.e. resistance to ciprofloxacin predicted resistance to all the quinolones tested in every case. This data demonstrates that fluoroquinolones are active agents against P. aeruginosa. In vitro susceptibility testing, however, is crucial to assess the resistance pattern in any specific location and for each individual agent.