新喹诺酮类药物在治疗结核病中的应用

经参考大量文献,对新喹诺酮类药物(本研究将第三、四代统称为新喹诺酮类药物)在治疗结核病中的应用情况进行探讨。新喹诺酮类药物具有良好抗结核作用,是一种使用安全、副反应小的新一代的抗结核药物。但存在一系列不良反应,应注意选择适应病例,通过皮试、控制用药剂量、给药速度、药物配伍等进行防范。     

Diagnosis, treatment and prevention of spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis (SBP) is a frequent complication in cirrhotic patients with ascites. Diagnosis of SBP is established by a polymorphonuclear cell count in ascitic fluid > or =250 cells/mm(3). The organism responsible for the infection is isolated in 60-70% of the cases. The remaining cases are considered to have a variant of SBP (culture-negative SBP) and are treated in the same way as those with a positive culture. The SBP resolution rate ranges between 70 and 90%, and hospital survival between 50 and 70%. An early diagnosis and the use of a more adequate antibiotic therapy are the most probable reasons for the improvement in prognosis for SBP in recent decades. Despite the resolution of the infection, SBP may trigger severe complications such as renal impairment, gastrointestinal bleeding and accentuation of hepatic insufficiency which are responsible for the associated mortality. Patients recovering from an episode of SBP should be considered as potential candidates for liver transplantation.     

Intracranial Nocardia recurrence during fluorinated quinolones therapy

Nocardia infection is a well-recognized complication in renal transplant recipients and other immunocompromised hosts. It is mostly a primary pulmonary infection, which can disseminate to other organs in half of the cases. Nocardiosis is a life-threatening infection. Therefore, an efficient long-lasting treatment must be rapidly administered. We report 1 case of disseminated nocardiosis with pulmonary involvement, brain lesions, and bone lesions in a renal transplant patient, who was treated with stereotactic aspiration in association with high dose of trimethoprim/sulfamethoxazole (TMP/SMX) and imipenem, changed, after 3 weeks to moxifloxacin. First, clinical manifestations decreased after surgical drainage and combination therapy with the 2 antimicrobial agents, but later the patient developed a recurrence of brain lesions during treatment with quinolones. Consequently, the patient was again treated with TMP/SMX and imipenem, after which the patient recovered. It is surprising that moxifloxacin was efficient in vitro and the antimicrobial concentration in the central nervous system was high, yet the nocardial abscess recurred under this therapy.     

AcrAB外排泵ramA对肺炎克雷伯菌耐喹诺酮类药物的影响

目的 探讨AcrAB外排泵调控基因ramA对肺炎克雷伯菌耐喹诺酮类药物的影响。方法 用喹诺酮类药敏纸片扩散法、MIC及其逆转实验和有机溶剂耐受实验测定细菌耐药表型,用PCR扩增外排泵结构基因acrA、acrB、tolC及调控基因acrR,ramA,marA,用半定量PCR 检测调控基因的转录水平。结果 泵的结构基因和调控基因均存在43株KP菌中。仅喹诺酮类耐药株与敏感株ramA转录水平存在统计学差异(P<0.05)。和对照组相比,高表达ramA的 AC-1株,其泵结构基因的转录水平增高,耐药表型也有明显改变,用泵抑制剂后,其喹诺酮类的MIC恢复对照水平。结论 ramA是KP菌耐喹诺酮类抗生素的一个重要因素。抑制ramA的表达,有助于治疗多重耐药肺炎克雷伯菌的感染。     

人型支原体对8种药物的敏感性及喹诺酮类药物耐药基因gyrA突变的研究

目的：检测人型支原体(Mh)对8种药物的敏感性，并检测喹诺酮类药物耐药株gyrA基因突变情况。方法：应用微量肉汤稀释法检测Mh对8种药物的敏感性，用PCR和DNA测序及序列比较检测基因突变。结果：大环内酯类药物中只有交沙霉素抗Mh活性较强，MIC50和MIC90分别为0．25μg／ml和0．5μg／ml，四环素类药物中多西环素的抗Mh活性优于四环素，MIC50仅为0．06μg／ml，MIC90仅为1μg／ml；喹诺酮类药物环丙沙星和氧氟沙星的抗Mh活性较强。基因序列分析表明gyrA基因碱基113位C到T的突变为有义突变，导致所编码的83位丝氨酸被亮氨酸替代，其余均为同义突变。结论：8种药物中以交沙霉素、多西环素、环丙沙星和氧氟沙星的抗Mh的活性较强；gyrA基因113位碱基C到T的突变与Mh耐喹诺酮类药物密切相关。     

In vitro quinolone-gentamicin antagonism demonstrated by time-kill and combination experiments with clinical isolates ofEnterococcus

Bacteriostatic and bactericidal activites of amoxicillin, pefloxacin, ofloxacin, ciprofloxacin, sparfloxacin, vancomycin, alone or associated with gentamicin, were evaluated over 22 months using time-kill and combination experiments, on 20 clinicalEnterococcus isolates (6E. faecium and 14E. faecalis) selected in a French district hospital. Sparfloxacin or ciprofloxacin were more frequently bacteriostatic or bactericidal than pefloxacin or ofloxacin but, unlike amoxicillin or vancomycin, the association with gentamicin was not synergistic in most cases and antagonisms were observed in some cases. These results suggest that the use of sparfloxacin or ciprofloxacin could be considered in some cases of infections withEnterococcus that are resistant to penicillins and glycopeptides and/or highly resistant to aminoglycosides. Despite Perri's report to the contrary, the effect of quinolones and gentamicin in combination use was not only synergistic but antagonistic, and we are alerting others to the possible antagonism involved.     

In vitro evaluation of the activity of β-lactams,new quinolones,and other antimicrobial agents againstStreptococcus pneumoniae

The in vitro activities of the β-lactam and quinolone antibiotics panipenem, cefpodoxime, cefdinir, cefditoren, faropenem, tosufloxacin, levofloxacin and grepafloxacin were compared with similar conventional antibiotics against penicillin-resistantStreptococcus pneumoniae (PRSP). Pneumococcal isolates collected from October 1994 to March 1995 (n=1283) consisted of penicillin-susceptibleS. pneumoniae (PSSP; 59.2%), penicillin-intermediately-resistantS. pneumoniae (PISP;11.2%), and PRSP (29.6%). The isolates were highly susceptible to panipenem, faropenem and cefditoren with MIC₉₀ values of 0.125 μg/mL, 0.5 μg/mL and 0.5 μg/mL, respectively. Correlation coefficients for the relationships between the MICs of these β-lactam agents and that of penicillin G ranged from γ=0.7652 to γ=0.8022. These new β-lactam agents produced excellent bactericidal responses at concentrations greater than their MICs for PSSP concomitant with appropriate cellular morphologic changes. However, the bactericidal action of these antibiotics against PRSP was less pronounced and fewer instances of cell lysis were observed. The MIC₉₀ of cefpodoxime was similar to that of cefaclor, whereas that of cefdinir was between those of faropenem and cefpodoxime. The MIC distribution of the new quinolone agents showed 1 peak, but the MIC₉₀ values of tosufloxacin and grepafloxacin were both 0.5 μg/mL and that of levofloxacin was 2.0 μg/mL. Only 1% of all isolates demonstrated cross-resistance to all quinolone agents.     

通过喹诺酮抗生素与磷脂膜的相互作用预测肺泡巨噬细胞单层的体外摄取

目的;预测肺泡巨噬细胞单层的体外摄取.方法:以培养的肺泡巨噬细胞单层为体外模型,用磷脂膜色谱,脂质体/水系统评价药物与磷脂膜的相互作用,分别表示为lg k_(1AM),lg D_(L B,7.4),用正辛醇/水系统测定参考的疏水性参数(lg D_(O/B,7.4).结果:lg D_(L B,7.4)(r~2=0.93)比lg D_(O B,7.4)(r~2=0.65)具有与lg k_(1AM)更显著的相关性.lg k_(1AM)和lg D_(L B,7.4)均 比lg D_(O/B,7.4)与细胞内药物的蓄积度有更好的相关性.但对于由5个两性喹酮抗生素和奎尼丁组成的受试集合,三者均与药物进入细胞内的速度具有相近的显著的正相关性.结论:磷脂膜色谱和脂质体/水系统给出相似的亲脂性测量尺度,且均与正辛醇/水系统区别有显著性.与疏水性参数相比,膜亲和性是更有效的肺泡巨噬细胞内药物蓄积和结合的预测参数.     

In Vitro Activity of Lomefloxacin (SC-47111) Against Enterobacteriaceae,Enterococci and Staphylococci

Summary

The activity of lomefloxacin, a new difluorinated quinolone, was tested against 190 Enterobacteriaceae strains (belonging to 23 different species), 70 enterococci and 70 staphylococci. As regards Enterobacteriaceae, the activity of lomefloxacin was the same as that of norfloxacin in 9 out of the 23 species tested, and only slightly lower in further 8 species. Minimum inhibitory concentrations (MIC) values for 90% of strains were 0.5 μg/ml in 2 species, 0.25 μg/ml in 6, 0.125 μg/ml in 4, and lower than 0.125 μg/ml in 8. Slightly higher values were obtained for Serratia marcescens (2 μg/ml), whilst, as already reported for the other new quinolones, the susceptibility of the Providencia genus was very poor, with MIC values up to 128 μg/ml for the vast majority of strains. Lomefloxacin proved bactericidal at the MIC in all the Enterobacteriaceae strains tested but 20. In the latter strains, however, bactericidal activity could be appreciated at values slightly exceeding MIC. As regards enterococci, the MIC for 90% of strains was 32 μg/ml. Minimum bactericidal concentration (MBC) was the same as the MIC for 78% of the strains tested and was only twofold higher in all the others. The new drug was also active against staphylococci having an MIC50 and MIC₉₀ of 0.5 and 2 μg/ml, respectively. It was bactericidal at the MIC for 62% of the strains and at twofold the MIC for all the others.