左氧氟沙星联合万古霉素缩小金黄色葡萄球菌耐药突变选择窗的初步研究

目的:在体外初步探讨联合用药可缩小单药对细菌的耐药突变选择窗(MSW),为临床合理使用现有抗菌药物,防止细菌耐药产生提供理论依据。方法:应用肉汤法富集1010CFU/mL细菌,琼脂平板二倍稀释法测定左氧氟沙星、万古霉素单药和两药联用对金黄色葡萄球菌ATCC29213的最低药物浓度(MPC)和MSW。结果:左氧氟沙星、万古霉素单药对金黄色葡萄球菌ATCC29213的MSW分别为16和64。万古霉素和左氧氟沙星联合用药(1MIC 8MIC,2MIC 4MIC)使左氧氟沙星单药对ATCC29213的MSW缩小2～4倍。左氧氟沙星联合万古霉素用药(1MIC 16MIC,2MIC 8MIC)使万古霉素对ATCC29213的MSW缩小4～8倍。结论:万古霉素和左氧氟沙星联合用药可缩小各自单药对金黄色葡萄球菌ATCC29213的MSW。     

中药影响左氧氟沙星对金黄色葡萄球菌的耐药突变选择窗的初步研究

目的:研究中药在左氧氟沙星对金黄色葡萄球菌耐药突变选择窗(MSW)上的影响。方法:采用琼脂平板稀释法测定几种中药制剂的最低抑菌浓度(MIC)、防突变浓度(MPC),得出其选择指数(SI)。选择SI值较低的中药制剂双黄连与大蒜素分别与左氧氟沙星联用,琼脂平板稀释法测定不同浓度下双黄连/大蒜素与左氧氟沙星联用对金黄色葡萄球菌MSW上的影响。结果:双黄连和左氧氟沙星联用(2MIC+8MIC,4MIC+4MIC)可使左氧氟沙星对金黄色葡萄球菌的MSW缩小至0.4～0.8倍;而不同浓度大蒜素与左氧氟沙星联用,则未见明显作用。结论:双黄连注射剂与左氧氟沙星联用可缩小左氧氟沙星对金黄色葡萄球菌的MSW,从而降低金黄色葡萄球菌对左氧氟沙星的耐药性。     

Microbiological outcome of complicated urinary tract infections treated with levofloxacin: a pharmacokinetic/pharmacodynamic analysis

The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined in patients with complicated urinary tract infections (UTIs) treated with 500 mg of levofloxacin every 24 h for 7–14 days. Of 241 pre-treatment strains from 156 patients, 21 strains persisted after treatment. In each patient, plasma concentrations of levofloxacin were simulated based on population pharmacokinetic parameters and patient-specific data. Minimum inhibitory concentrations (MICs) of levofloxacin for the pre-treatment strains determined in our previous study were used. The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined by logistic regression analyses. For all the isolates, Gram-negative bacilli, Gram-positive cocci, Escherichia coli and Enterococcus faecalis, the target values of the area under the concentration–time curve (AUC)/MIC were 14.65, 31.46, 4.85, 43.00 and 3.06, respectively, and the targets of the maximum plasma concentration (C_max)/MIC were 1.22, 2.74, 0.39, 3.61 and 0.25, respectively. Such thresholds of AUC/MIC and C_max/MIC in complicated UTIs would be lower than those in infections of other sites. In particular, the C_max/MIC thresholds for Gram-positive cocci and E. faecalis were <1. These findings suggested that, in addition to its plasma concentration, the high concentration of levofloxacin in the urine might play a role in eradicating bacteria.     

甲磺酸加替沙星与其他4种氟喹诺酮类药物对临床分离菌的体外抗菌活性比较

目的 :比较甲磺酸加替沙星与氧氟沙星、左氧沙星、环丙沙星、司帕沙星对 182株临床分离菌的体外抗菌活性。方法 :采用琼脂平板二倍稀释法测定加替沙星等 5种氟喹诺酮类药物对 182株临床试验分离菌株的最低抑菌浓度 (MIC)。结果 :加替沙星对葡萄球菌属的MIC90 比其他 4种氟喹诺酮类药物低。葡萄球菌属对加替沙星的敏感率显著高于其他4种氟喹诺酮类药物 ;对其他G 球菌的MICR 也较其他氟喹诺酮类药物低。G-杆菌中埃希菌属、肠杆菌属对加替沙星的敏感率明显高于其他 4种氟喹诺酮类药物 ,加替沙星对埃希菌属、肠杆菌属的MIC90比左氧沙星低 2倍 ,比其他 3种抗菌药物低 8倍 ;假单胞菌属、克雷伯菌属和其他G-杆菌对加替沙星的敏感率与左氧沙星的差异无统计学意义 ,与其他 3种氟喹诺酮类药物的差异有统计学意义。结论 :甲磺酸加替沙星具有广谱而强大的体外抗菌活性。     

Tissue and serum concentrations of levofloxacin in orthopaedic patients.

The level of levofloxacin was determined in serum, bone and several tissues after a single dose of 500 mg i.v. Twenty-one patients (mean age: 56.8 years) undergoing bone surgery (nine patients) or surgical debridement of a decubitus ulcer (12 patients) who received levofloxacin as perioperative prophylaxis were included in the study. During surgery, blood and tissue samples were obtained approximately 1.5 h (range 40-210 min) postdosing. Levofloxacin concentrations in 87 specimens including 21 serum samples were determined using high-performance liquid chromatography (HPLC). The mean serum concentration at 1.5 h was 8.6+/-2.3 microg/ml. Concentrations above the MIC of common pathogens were reached in all tissues during the collection period with a maximum in skin samples (19.9+/-9.9 microg/g) followed by wound tissue and granulation tissue with 17.3+/-6.5 and 13.7+/-6.4 microg/g respectively. In muscle and fatty tissue mean levofloxacin concentrations of 8.0+/-0.9 and 4.0+/-2.2 microg/g were attained. Mean levels in cancellous bone were 6.6+/-3.6 microg/g, lowest levels were measured in cortical bone (2.8+/-1.1 microg/g). Twenty-two different pathogens were cultivated from the lesions of 11 of 12 patients with pressure ulcers. MIC values for levofloxacin were determined and compared with the corresponding tissue concentrations. Levofloxacin may be useful for perioperative prophylaxis and treatment in orthopaedic patients due to its good tissue penetration.     

双黄连联合左氧氟沙星对耐甲氧西林金黄色葡萄球菌的体外抗菌活性

目的:评价双黄连与左氧氟沙星联合应用耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌作用。方法:采用棋盘法设计,微量肉汤稀释法测定其MIC值,计算FIC指数。结果:左氧氟沙星与双黄连联合应用后,左氧氟沙星对MRSA的MIC值均有下降。同样,双黄连对MRSA的MIC值亦有下降。FIC指数范围主要在0~1。结论:左氧氟沙星与双黄连联合应用,对MRSA的体外联合抗菌作用主以相加为主。     

A novel colorimetric broth microdilution method to determine the minimum inhibitory concentration (MIC) of antibiotics and essential oils against Helicobacter pylori

Helicobacter pylori infections have been associated with the pathogenesis of a number of stomach and gastroduodenal diseases. In order to find alternative drugs for their treatment the search is increasingly focused on new antimicrobial products. However, no standardized methods are available to test the anti-Helicobacter pylori activity in particular of natural substances. Therefore we developed a broth microdilution assay to investigate the susceptibility of this fastidious slow growing bacterium against 15 essential oils widely used to treat disorders of the gastrointestinal tract. The MIC values were determined colorimetrically using p-iodonitrophenyltetrazolium violet (INT) as an indicator for bacterial cell viability. The test sytem was evaluated with three common antibiotics: amoxicillin, ampicillin and levofloxacin. The antibiotic MICs were controlled by Etest. The Helicobacter reference strain was remarkably susceptible to both the antibiotics (amoxicillin MIC: 0.02 microg/ml, ampicillin MIC: 0.064 microg/ml, levofloxacin MIC: 0.39 microg/ml) and the essential oils. Most of their MICs ranged from 0.015 to 0.064% (v/v) and about 140.0 to 280.0 microg/ml, respectively. Interestingly, chamomile oil, orange flower oil and ginger oil inhibited the bacterial growth in extraordinarily low concentrations of 0.0075% (v/v) and about 65 microg/ml, respectively. The bactericidal concentrations were generally one to two dilution steps higher. In conclusion, we could develop an innovative assay for the MIC determination of essential oils and antibiotics against Helicobacter pylori, which is simple to handle, accurate, reproducible and not as time- and material-consuming as traditional agar dilution techniques.     

Comparative in vitro activity and pharmacodynamics of five fluoroquinolones against clinical isolates of Streptococcus pneumoniae

STUDY OBJECTIVE: To compare in vitro activity and pharmacodynamics of five fluoroquinolones against clinical isolates of Streptococcus pneumoniae. DESIGN: In vitro analysis. SETTING: University research laboratory. INTERVENTION: Minimum inhibitory concentrations (MICs) were determined for penicillin and five fluoroquinolones by E test for 201 S. pneumoniae isolates. Serum concentration-time profiles were simulated for the following regimens: ciprofloxacin 750 mg orally every 12 hours and 400 mg intravenously every 8 hours; levofloxacin 500 mg orally and intravenously every 24 hours; trovafloxacin 200 mg orally and intravenously every 24 hours; gatifloxacin 400 mg orally and intravenously every 24 hours; and clinafloxacin 200 mg orally and intravenously every 12 hours. MEASUREMENTS AND MAIN RESULTS: Free 24-hour areas under the serum concentration-time curves (AUC0-24) were calculated using the trapezoidal rule, and the average AUC0-24:MIC ratio was calculated for each regimen. Differences in ratios among agents were determined by analysis of variance (Scheffe post hoc test, p < 0.05). For intravenous dosing, the average AUC0-24:MIC for gatifloxacin, clinafloxacin, trovafloxacin, ciprofloxacin, and levofloxacin was 146, 142, 122, 71, and 61, respectively. For both oral and intravenous regimens, gatifloxacin and clinafloxacin ratios were significantly greater than those for trovafloxacin, levofloxacin, and ciprofloxacin (p < or = 0.007). Ratios for trovafloxacin were significantly greater than those for levofloxacin and ciprofloxacin (p < 0.0001), and levofloxacin and ciprofloxacin ratios were not significantly different from each other. CONCLUSION: Gatifloxacin and clinafloxacin achieve significantly higher AUC0-24:MIC ratios for S. pneumoniae than trovafloxacin, levofloxacin, and ciprofloxacin. Large comparative studies are necessary to determine the clinical significance of these findings.     

Comparative efficacies of levofloxacin and ciprofloxacin against Streptococcus pneumoniae in a mouse model of experimental septicaemia.

The in vivo efficacies of levofloxacin and ciprofloxacin were compared against three clinical isolates of Streptococcus pneumoniae, using a mouse protection model. Two strains (SP 22 and SP 28) were penicillin-sensitive while one strain (SP 46) was penicillin-resistant. Each strain had identical susceptibility to both drugs. Using mice with renal impairment induced by uranyl nitrate injection, the elimination half-life of each antibiotic was prolonged to approximate human pharmacokinetic profiles of the drugs. The dosing regimen of each drug that yielded serum levels in mice which mimic human therapeutic concentrations of the drugs, were designed. One hour after intraperitoneal inoculation with minimum lethal dose of each strain, either levofloxacin at a dosing regimen of 10.6 mg/kg every 8 h or ciprofloxacin at 9.5 mg/kg every 8 h was subcutaneously administered for a total of six or 15 doses. In treatment, monitored daily for 5-8 days, levofloxacin resulted in higher survival compared with ciprofloxacin for the three strains. For example, percent survival following levofloxacin treatment recorded at day 4 postinfection with SP 22, SP 28 and SP 46 were 41, 90 and 30%, respectively, while the corresponding values after ciprofloxacin treatment were 27, 75 and 16%, respectively. However, statistical analysis did not reveal a significant difference (p > 0.05). The lack of significant difference observed in the efficacies of both drugs reflected the comparability of their 24-h AUC/MIC ratios. It is suggested that, with some strains of S. pneumoniae, the efficacy of levofloxacin may be equivalent to that of ciprofloxacin in the treatment of systemic pneumococcal infections caused by susceptible strains of the organism.     

Pharmacodynamic analysis of ceftriaxone, gatifloxacin,and levofloxacin against Streptococcus pneumoniae with the use of Monte Carlo simulation

STUDY OBJECTIVE: To evaluate the pharmacodynamics of four intravenous antimicrobial regimens-ceftriaxone 1 g, gatifloxacin 400 mg, levofloxacin 500 mg, and levofloxacin 750 mg, each every 24 hours-against recent Streptococcus pneumoniae isolates. DESIGN: Pharmacodynamic analysis using Monte Carlo simulation. DATA SOURCE: The Surveillance Network (TSN) 2002 database. MEASUREMENTS AND MAIN RESULTS: Streptococcus pneumoniae isolates (7866 isolates) were stratified according to penicillin susceptibilities as follows: susceptible (4593), intermediate (1986), and resistant (1287). Risk analysis software was used to simulate 10,000 patients by integrating published pharmacokinetic parameters, their variability, and minimum inhibitory concentration (MIC) distributions from the TSN database. Probability of target attainment was determined for percentage of time above the MIC (%T > MIC) from 0-100% for ceftriaxone and area under the concentration-time curve (AUC):MIC ratio from 0-150 for the fluoroquinolones. For ceftriaxone, probability of target attainment remained 90% or greater against the three isolate groups until a %T > MIC of 70% or greater, and it remained 90% or greater against susceptible and intermediate isolates over the entire interval (%T > MIC 0-100%). For levofloxacin 500 mg, probability of target attainment was 90% at an AUC:MIC < or = 30, but the curve declined sharply with further increases in pharmacodynamic target. Levofloxacin 750 mg achieved a probability of target attainment of 99% at an AUC:MIC ratio < or = 30; the probability remained approximately 90% until a target of 70 or greater, when it declined steeply. Gatifloxacin demonstrated a high probability (99%) of target attainment at an AUC:MIC ratio < or = 30, and it remained above 90% until a target of 70. CONCLUSION: Ceftriaxone maintained high probability of target attainment over a broad range of pharmacodynamic targets regardless of penicillin susceptibility (%T > MIC 0-60%). Levofloxacin 500 mg maintained high probability of target attainment for AUC:MIC ratios 0-30; whereas, levofloxacin 750 mg and gatifloxacin maintained high probability of target attainment for AUC:MIC ratios 0-60. Rate of decline in the pharmacodynamic curve was most pronounced for the two levofloxacin regimens and more gradual for gatifloxacin and ceftriaxone.     

Where should antibiotic gradient diffusion strips be crossed to assess synergy? A comparison of the standard method with a novel method using steady-state antimicrobial concentrations

Multi-drug resistance among Pseudomonas aeruginosa in hospitals, and particularly intensive care units, has achieved alarming rates. Some combination antimicrobial therapies have demonstrated promising synergistic effects and an ability to overcome resistance without increasing drug-related toxicities. Nevertheless, rapid and feasible methods to identify synergy have not been routinely implemented in clinical microbiology laboratories.Synergistic activity of meropenem plus tobramycin or levofloxacin against clinical P. aeruginosa isolates (N=21) was assessed by two different methods using gradient diffusion strips (GDSs). A 90° angle was created at the intersection of the minimum inhibitory concentration (MIC) of each drug by the standard method, and by a novel method, the cross was placed at clinically relevant steady-state concentrations (C_ss) based on recommended dosing regimens. Fractional inhibitory concentration indexes were determined to describe antibiotic interactions. Time-kill analyses were performed over 24 h in duplicate for instances of discordance between the standard cross method and the novel method.Synergy between meropenem and tobramycin by the novel method was observed in one (4.8%) isolate and between meropenem and levofloxacin in two (9.5%) isolates. Agreement with the standard method was 86–100% for meropenem plus tobramycin and meropenem plus levofloxacin combinations, respectively. Time-kill studies resulted in agreement with GDSs crossed at C_ss in two of three instances of discordance between GDS methods.This novel method of synergy testing that involves crossing GDSs at steady-state concentrations may be a rapid and feasible tool for routine practice. Further comparisons of this novel procedure with time-kill methods are needed.     

左氧沙星与磷霉素联用对金黄色葡萄球菌的体外杀菌活性研究

目的：评价左氧沙星与磷霉素联用对金黄色葡萄球菌的联合抗菌效应。了解左氧沙星单用及与磷霉素联用的杀菌曲线特点。方法：选取3株MSSAATCC29213、临床分离菌SA99、SARN450（实验室菌株）和1株临床分离的MRS-AB6177,采用菌落计数法对不同浓度的左氧沙星或磷霉素单用及两药联合对3株MSSA和1株MRSA进行体外杀菌实验。结果：左氧沙星的杀菌曲线表现出浓度依赖性,磷霉素的杀菌曲线表现出非浓度依赖性。两药1/4MIC浓度单用时虽然均无法抑制MSSA的生长,而两药亚抑菌浓度联合使用后即表现出协同效应和杀菌效应。两药4MIC、8MIC联合时对MRSA表现出杀菌效应。结论：亚抑菌浓度的左氧沙星与磷霉素联合对MSSA即可出现协同杀菌效应。左氧沙星联合磷霉素对MRSA也表现出显著的杀菌活性。     

Prevention of the selection of resistant Staphylococcus aureus by moxifloxacin plus doxycycline in an in vitro dynamic model: an additive effect of the combination

Twenty-four hour ratios of area under the curve (AUC(24)) to MIC of 200-240 h providing quinolone concentrations above the mutant prevention concentration (MPC) protected from enrichment of resistant Staphylococcus aureus in our recent study that simulated the pharmacokinetics of moxifloxacin, gatifloxacin, levofloxacin and ciprofloxacin. These protective AUC(24)/MICs might also be achieved by using antibiotic combinations, assuming additive effects of two anti-staphylococcal agents. To test this hypothesis, changes in S. aureus susceptibility were examined in a dynamic model that simulates 5-day treatment with moxifloxacin and doxycycline, alone and in combination at sub-optimal AUC(24)/MICs of each agent. Significant increases in MIC were observed with monotherapy where moxifloxacin or doxycycline concentrations fell into the mutant selection window (MSW) for more than 80% of the dosing interval (AUC(24)/MIC 60 h). Less pronounced changes in MIC occurred when the summed concentrations of moxifloxacin (AUC(24)/MIC 30 and 60 h) and doxycycline (AUC(24)/MIC 30 and 60 h) were inside the MSWs for the individual drugs for 30-50% of the dosing interval. No loss in susceptibility was found at moxifloxacin or doxycycline AUC(24)/MIC 170 h combined with the smaller AUC(24)/MIC (60 h) of the second compound. These data suggest that the total AUC(24)/MIC of 230 h might protect against S. aureus resistance. As this value is very close to that predicted in monotherapy with moxifloxacin (220 h), an additive protective effect of quinolone+doxycycline on the selection of resistant S. aureus is proposed. The use of drug combinations may be useful for restricting the enrichment of resistant mutants with agents whose clinically achievable AUC(24)/MICs do not provide concentrations above the MPC.     

Antibacterial effects of moxifloxacin and levofloxacin simulating epithelial lining fluid concentrations against community-acquired methicillin-resistant Staphylococcus aureus

BACKGROUND AND OBJECTIVE: Current North American guidelines advocate the use of respiratory fluoroquinolones for the empirical management of community-acquired pneumonia (CAP). While community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a pathogen frequently encountered in skin and skin structure infections, it has also now been recognised as a causative pathogen in CAP. Since fluoroquinolones may be used empirically to treat unsuspected CA-MRSA pneumonia, the objective of this study was to evaluate the antibacterial properties of levofloxacin and moxifloxacin using human simulated drug exposures in epithelial lining fluid (ELF). METHODS: An in vitro model was used to simulate the ELF concentrations, previously determined in older adults receiving multiple doses, of levofloxacin 500 mg once daily and moxifloxacin 400mg once daily. Four CA-MRSA isolates were studied at a starting inoculum of 10(6) colony-forming units (CFU)/mL; selected isolates were also studied at 10(8) CFU/mL. Bacterial density and resistance were quantitatively assessed over 48 hours. Drug exposure (area under the concentration-time curve [AUC]) was confirmed using validated drug assays. RESULTS: At a standard 10(6) starting inoculum, sustained bacterial kill (3.6-4.5 log) with both fluoroquinolones was noted for CA-MRSA isolates 27 and 44 (AUC/minimum inhibitory concentration [MIC] = 383-3923). Despite an MIC of 8 microg/mL (AUC/MIC = 25) for isolate 3, levofloxacin displayed a 2.8 log kill, while moxifloxacin (MIC 1 microg/mL) sustained a 4.5 log kill (AUC/MIC = 207) over 48 hours. Against isolate 59, levofloxacin displayed no antibacterial effect (AUC/MIC = 3), while moxifloxacin with an MIC of 8 microg/mL (AUC/MIC = 31) killed 4.6 log. At a high inoculum (10(8)), both fluoroquinolones showed 5.2-5.6 log kill for the susceptible isolate (44), while moxifloxacin showed no antibacterial activity against isolate 59. Drug exposure (AUC/MIC) appeared to correlate well (r(2) = 0.99) with the change in log CFU/mL. Maximal activity was observed for both drugs at an AUC/MIC of approximately 30. CONCLUSION: When evaluated at human simulated ELF concentrations, both levofloxacin and moxifloxacin appeared to demonstrate sustained antibacterial activity for CA-MRSA isolates with MICs 相似文献   

Variations in serotypes and susceptibility of adult non-invasive Streptococcus pneumoniae isolates between the periods before (May 2000-May 2001) and 10 years after (May 2010-May 2011) introduction of conjugate vaccines for child immunisation in Spain

This study explored the serotype distribution and antibiotic susceptibility of adult non-invasive Streptococcus pneumoniae isolates received in the Spanish Reference Laboratory for Pneumococci immediately prior to introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in June 2001 (May 2000-May 2001) and 10 years afterwards (May 2010-May 2011). Serotyping was performed by Quellung reaction and/or dot-blot assay, and minimum inhibitory concentrations (MICs) were determined by agar dilution. Clinical and Laboratory Standards Institute (CLSI) breakpoints were used for susceptibility interpretation. A total of 1274 isolates were identified (650 in the first period and 624 in the second period). PCV7 serotypes (as a group) showed a decrease (P<0.001) from 43.2% in the first period to 13.9% in the second period, with MIC(90) values (MIC for 90% of the organisms) of levofloxacin for the remaining PCV7 serotypes of 16 μg/mL. Inversely, non-PCV7 serotypes (as a group) increased from 56.8% to 86.1% (P<0.001), mainly due to increases in serotypes 19A (294.1% increase; P<0.001) and 15A (180.0% increase; P=0.005). Globally, non-susceptibility to penicillin decreased from 54.2% in the first period to 36.9% in the second period (P<0.001). Serotype 19A became the most worrisome, with an increase (at least five dilutions) in MIC(90) for all β-lactams in the second period, with non-susceptibility increasing from 18.2% to 71.4% (P=0.003) for penicillin and from 0.0% to 38.1% (P=0.022) for amoxicillin. Cefditoren showed the highest intrinsic activity (lowest MIC(50)/MIC(90)) overall and also against serotype 19A. Continuous surveillance of serotype distribution and antibiotic susceptibility among adult non-invasive isolates is necessary to detect emerging serotypes and to continuously assess the intrinsic activity of highly active oral antibiotics such as levofloxacin and cefditoren and of parenteral antibiotics such as cefotaxime.     

乳酸左氧氟沙星滴眼液在兔眼房水中的药代动力学

目的 :测定乳酸左氧氟沙星 (LVFX)滴眼液单次滴眼后不同时间兔眼房水的药物浓度 ,计算其药动学参数。方法 :取32只大白兔分为8组 ,各组于用药后0 125、0 25、0 50、0 75、1 0、2 0、3 0、4 0h取眼房水 ,用高效液相色谱法测定药物浓度。结果 :用3p87药动学程序拟合符合一室开放模型 ,药物在房水中Tmax0 940h、Cmax 0 592μg/ml、T1/2(Ka)0 479h、T1/2(Ke)0 919h。结论 :单次滴眼后兔房水中LVFX峰浓度均高于大多数致病菌的MIC90,LVFX滴眼液可用于眼内感染的临床治疗和预防。     

In vitro activity against aerobes and anaerobes of trospectomycin versus spectinomycin.

The general antibacterial properties of trospectomycin (TRO) were compared with those of spectinomycin (SPEC) in an in vitro study using a collection of recent clinical isolates: 50 Gram-positive and 25 Gram-negative aerobes and 30 Gram-positive and 15 Gram-negative anaerobes. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined for all strains by microtitre using serial dilutions in Mueller-Hinton broth for aerobes and Brucella broth for anaerobes. The final inoculum in each well was 10(5) cfu/ml. This study shows that none of the Gram-negative organisms was sensitive to TRO; the most sensitive were streptococci aerobic strains; TRO exhibited antibiotic activity against all anaerobes tested, which was not seen with SPEC, and also exhibited bactericidal activity. The MICs of Staphylococcus epidermidis and Bacteroides fragilis tested with TRO and SPEC were not significantly affected by the size of bacterial inoculum tested, and the nature of the growth medium did not alter the susceptibility tests.     

左氧氟沙星治疗细菌性角结膜炎的疗效

目的：验证0．3％盐左氧氟沙星商眼对细菌性角膜炎和结膜炎的疗效。方法：试验组31例用左氧氟沙星滴眼液,对照组31例用氧氟沙星滴眼液,观察疗效和不良反应,测定2药对结膜囊或角膜病灶分泌物细菌培养分离菌的敏感率和MIC。结果：2药疗效无差异,但试验组疗程明显短对于对照组（P＜0．05）。左氧氟沙星对分离菌的MIC极著地低于氧氟沙星的MIC值（P＜0．01）。结论：0．3％盐酸左氧氟沙星滴眼液具有抗菌谱广、活性高、使用安全等特点,是治疗细菌性角膜炎和细菌性结膜炎的良好药物。     

Comparative in vitro bacteriostatic and bactericidal activity of trovafloxacin, levofloxacin and moxifloxacin against clinical and environmental isolates of Legionella spp.

The susceptibility of 140 Legionella spp isolates (106 clinical and 34 environmental isolates) to trovafloxacin (TRFX), levofloxacin (LEVX), moxifloxacin (MOFX), ciprofloxacin (CIPX), ofloxacin (OFLX), erythromycin (ERY), azithromycin (AZI) and rifampicin (RIF) was studied using a standard microdilution method and buffered yeast extract broth (BYE) supplemented with 0.1% alpha-ketoglutarate. The post-antibiotic effects (PAEs) of the study drugs against 10 clinical isolates of Legionella pneumophila sg.1 were compared. The MIC inhibiting 90% of strains tested on BYEalpha broth were 0.008, 0.016, 0.016, 0.06, 0.125, 0.5, 0.5, and 0.004 mg/l for TRFX, LEVX, MOXX, CIP, OFLX, ERY, AZI, and RIF, respectively. The MBC/MIC ratios ranged from one to eight depending on the antibiotic tested: TRFX [1x-2 x MIC], LEVX, MOFX, CIPX and OFLX [1x-4 x MIC], RIF [2x-4 x MIC], ERY and AZI [2x-8 x MIC]. TRFX, RIF, LEVX, MOFX, CIPX, OFLX, ERY and AZI showed similar activity against Legionella species other than L. pneumophila. One-hour exposures to the study antimicrobial agents at a concentration of 4 x MIC resulted in PAEs as follows (average in hours): TRFX: 2.68 h; RIF: 2.63 h; CIPX: 2.62 h; MOFX: 2.56 h; LEVX: 2.41 h; OFLX: 2.25 h; AZI: 1.65 h; and ERY: 1.54 h. In conclusion, our in vitro data confirm that trovafloxacin, levofloxacin, moxifloxacin and rifampicin have excellent bacteriostatic and bactericidal activity against Legionella spp and show significant post-antibiotic effect.     

利用MIC法筛选不同厂家生产的同一种抗菌药物

目的了解不同厂家生产的左氧氟沙星注射液和环丙沙星注射液的最低抑菌浓度（MIC），为临床医生合理选药提供依据。方法用琼脂稀释法和肉汤稀释法检测来自7个厂家的左氧氟沙星注射液和4种环丙沙星注射液对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌的MIC。结果同一种抗菌药物的MIC从0．06-4．0μg／mL不等，高低相差60倍以上（相差6个质控浓度）；7个厂家左氧氟沙星对铜绿假单胞菌的MIC从0．25～4．0μg／mL不等，高低相差16倍（相差4个质控浓度）。结论当一个医院同时存在多个厂家的同一种抗菌药物时，应该选用敏感性较高（MIC较低）的药物。