浙中地区幽门螺杆菌耐药性临床分析

目的分析浙中地区幽门螺杆菌临床分离菌株对常用抗生素的体外耐药情况及临床耐药特征。 方法选取2015年5月至2015年8月浙江省金华市中心医院胃镜标本中分离到的296株幽门螺杆菌菌株进行体外药敏试验,分析其对甲硝唑、左氧氟沙星、克拉霉素、呋喃唑酮、阿莫西林、庆大霉素和四环素等7种抗生素的幽门螺杆菌耐药情况。分别根据性别、年龄及疾病类型将所有病例分组。其中男性组139株,女性组157株;17~35岁组58株,36~55岁组157株,56~79岁组81株;上消化道炎症组212株,上消化道溃疡组84株。 结果在检测的296株幽门螺杆菌菌株中,甲硝唑耐药率最高（86.8%,257/296）,其次为左氧氟沙星（35.1%,104/296）和克拉霉素（22.3%,66/296）,阿莫西林、庆大霉素、呋喃唑酮和四环素未检测到耐药菌株,即耐药率均为0%。296株幽门螺杆菌菌株中,对7种抗生素全部敏感的菌株有37株,占为12.50%;单独耐药的菌株有132株,占44.60%（包括甲硝唑单独耐药130株、左氧氟沙星单独耐药1株、克拉霉素单独耐药菌株1株）;双重耐药菌株86株,占29.05%（包括左氧氟沙星+甲硝唑双重耐药62株、克拉霉素+甲硝唑双重耐药24株）;三重耐药的菌株41株,占13.85%（左氧氟沙星+克拉霉素+甲硝唑耐药）。同时,女性患者左氧氟沙星的耐药率高于男性患者（41.4% vs. 28.1%,χ²=5.760,P=0.016）;17~35岁、36~55岁及56~79岁年龄组左氧氟沙星的耐药率分别为19.0%、42.0%、33.3%,三组比较差异有统计学意义（χ²=10.052,P=0.007）,且17~35岁年龄组左氧氟沙星的耐药率明显低于36 ~ 55岁年龄组患者（P=0.002）。在炎症和溃疡患者中,左氧氟沙星耐药率（37.3% vs. 29.8%,χ²=1.486,P=0.223）、甲硝唑耐药率（86.3% vs. 88.1%,χ²=0.166,P=0.684）及克拉霉素耐药率（25.0% vs. 15.5%,χ²=3.150,P=0.076）的比较,差异亦均没有统计学意义。 结论浙中地区幽门螺杆菌菌株对甲硝唑、左氧氟沙星和克拉霉素耐药率高。且左氧氟沙星的耐药率明显与性别及年龄相关,应严格遵循抗生素治疗规范,并根据药敏结果进行个体化治疗,进而提高幽门螺杆菌的根除率。     

白光胃镜下胃黏膜形态变化对幽门螺杆菌感染的诊断价值分析

目的探究白光胃镜下胃黏膜形态变化对幽门螺杆菌（H. pylori）感染相关性胃炎的诊断价值。 方法回顾性分析2018年7月至2020年7月在海南医学院第二附属医院进行白光胃镜检查和13-尿素呼气试验（¹³C-UBT）检查的1160例病例,依据¹³C-UBT检查结果分为2组：H. pylori感染组（812例）和无H. pylori感染组（348例）。比较2组白光胃镜下胃粘膜形态差异,进行Logistic回归分析筛选出H. pylori感染独立相关的胃黏膜形态特征,并应用受试者工作特征曲线（ROC）评价相关指标的预测价值。 结果H. pylori感染组白光胃镜下弥漫性胃黏膜充血、点状发红、胃黏膜肿胀、胃体皱襞肿大蛇形、胃体黏膜呈“龟纹样”等检出率均显著高于无H. pylori感染组。多因素Logistic回归分析显示,弥漫性胃黏膜充血（OR=116.280）、点状发红（OR=4.821）、胃黏膜肿胀（OR=3.432）、胃体皱襞肿大蛇形（OR=4.336）、胃体黏膜呈“龟纹样”（OR=9.346）是H. pylori感染的独立相关因子。ROC曲线分析显示,弥漫性胃黏膜充血、点状发红、胃黏膜肿胀、胃体皱襞肿大蛇形、胃体黏膜呈“龟纹样”预测H. pylori感染的曲线下面积分别为0.829（95%CI：0.796~0.859）、0.687（95%CI：0.648~0.725）、0.750（95%CI：0.713~0.785）、0.578（95%CI：0.537~0.619）、0.619（95%CI：0.578~0.619）,其中以弥漫性胃黏膜充血、胃黏膜肿胀较大,它们的敏感度和特异度分别为93.68%和72.17%、97.13%、52.96%。 结论白光胃镜下胃黏膜形态变化与H. pylori感染具有相关性,以弥漫性胃黏膜充血、胃黏膜肿胀对H. pylori感染的诊断价值较大。     

CP6679, a new injectable cephalosporin with broad spectrum and potent activities against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa

 The antibacterial activities of CP6679, a new injectable cephalosporin with a broad antibacterial spectrum, were compared with those of other cephalosporins. CP6679 had stronger in-vitro activity than ceftazidime and cefpirome against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci, and Pseudomonas aeruginosa. Its activity against MRSA was eight times stronger than that of cefpirome, and it showed high binding affinity for penicillin-binding protein 2′ of MRSA. Furthermore, the antibacterial activity of CP6679 against ceftazidime-resistant and imipenem-resistant P. aeruginosa was eight times stronger than that of ceftazidime and four times stronger than that of imipenem. In addition to its in-vitro activities, CP6679 showed the highest efficacy among all cephalosporins tested in murine models of systemic infection induced by MRSA or P. aeruginosa. It was more effective than vancomycin and cefpirome against respiratory tract infections induced by MRSA in mice. Received: October 4, 2001 / Accepted: December 12, 2001     

In vitro and in vivo evaluations of A-80556, a new fluoroquinolone.

A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC for 90% of isolates [MIC90], 0.12 microgram/ml, relative to fluoroquinolone-susceptible strains) and Streptococcus pneumoniae (MIC90, 0.12 microgram/ml). A-80556 was also the most active of the quinolones tested against ciprofloxacin-resistant S. aureus, with an MIC90 of 4.0 micrograms/ml; that of ciprofloxacin was > 128 micrograms/ml. However, the significance of this activity is not known. A-80556 was slightly less active against Escherichia coli (MIC90, 0.06 microgram/ml) and other enteric organisms than ciprofloxacin (MIC90 for E. coli, < or = 0.03 microgram/ml). A-80556 was slightly less active against Pseudomonas aeruginosa (MIC90, 4.0 micrograms/ml) than ciprofloxacin (MIC90, 2.0 micrograms/ml) and more active against Acinetobacter spp. (respective MIC90s, 0.12 and 0.5 microgram/ml). A-80556 was also the most active compound against anaerobes. Against Bacteroides fragilis, the MIC90 of A-80556 was 2.0 micrograms/ml; that of ciprofloxacin was 16 micrograms/ml. The in vivo efficacy of A-80556 in experimental models with both gram-positive and gram-negative infections was consistent with the in vitro activity and pharmacokinetics and oral absorption in mice.     

In vitro and in vivo antibacterial activities of DC-159a, a new fluoroquinolone

DC-159a is a new 8-methoxy fluoroquinolone that possesses a broad spectrum of antibacterial activity, with extended activity against gram-positive pathogens, especially streptococci and staphylococci from patients with community-acquired infections. DC-159a showed activity against Streptococcus spp. (MIC(90), 0.12 microg/ml) and inhibited the growth of 90% of levofloxacin-intermediate and -resistant strains at 1 microg/ml. The MIC 90s of DC-159a against Staphylococcus spp. were 0.5 microg/ml or less. Against quinolone- and methicillin-resistant Staphylococcus aureus strains, however, the MIC 90 of DC-159a was 8 microg/ml. DC-159a was the most active against Enterococcus spp. (MIC 90, 4 to 8 microg/ml) and was more active than the marketed fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin. The MIC 90s of DC-159a against Haemophilus influenzae, Moraxella catarrhalis, and Klebsiella pneumoniae were 0.015, 0.06, and 0.25 microg/ml, respectively. The activity of DC-159a against Mycoplasma pneumoniae was eightfold more potent than that of levofloxacin. The MICs of DC-159a against Chlamydophila pneumoniae were comparable to those of moxifloxacin, and DC-159a was more potent than levofloxacin. The MIC 90s of DC-159a against Peptostreptococcus spp., Clostridium difficile, and Bacteroides fragilis were 0.5, 4, and 2 microg/ml, respectively; and among the quinolones tested it showed the highest level of activity against anaerobic organisms. DC-159a demonstrated rapid bactericidal activity against quinolone-resistant Streptococcus pneumoniae strains both in vitro and in vivo. In vitro, DC-159a showed faster killing than moxifloxacin and garenoxacin. The bactericidal activity of DC-159a in a murine muscle infection model was revealed to be superior to that of moxifloxacin. These activities carried over to the in vivo efficacy in the murine pneumonia model, in which treatment with DC-159a led to bactericidal activity superior to those of the other agents tested.     

In vitro and in vivo evaluation of DU6859a,a new fluoroquinolone,among injectable antibacterials tested against clinical isolates

DU6859a was evaluated for its in vitro and in vivo antibacterial activities in comparison with those of imipenem, meropenem, cefpirome, vancomycin, gentamicin, ciprofloxacin and levofloxacin. DU6859a had activity comparable to that of imipenem against methicillin-susceptible staphylococci and penicillin-susceptible and-resistantStreptococcus pneumoniae, with MICs at which 90% of strains tested are inhibited (MIC₉₀)≤0.063μg/mL. Against methicillin-resistant staphylococci and enterococci, DU6859a was as active as vancomycin and more active than other drugs tested, with MIC₉₀s ranging from 1 to 4 μg/mL. DU6859a was as active as ciprofloxacin and more active than other drugs tested against imipenem-resistantPseudomonas aeruginosa. Differences in activity between DU6859a and reference drugs against ciprofloxacin-resistant and gentamicin-resistantP. aeruginosa were particularly striking. The in vivo efficacy of subcutaneous injections of DU6859a against experimental septicemia, respiratory and pyelonephritic infections caused by gram-positive and-negative bacteria, including methicillin-resistantStaphylococcus aureus and imipenem-resistantP. aeruginosa, reflected its potent in vitro activity.     

In vitro and in vivo antibacterial activities of T-3262, a new fluoroquinolone.

T-3262, a new fluoroquinolone, showed a broad spectrum of activity against gram-positive and gram-negative bacteria. T-3262 had most potent activity against gram-positive cocci, such as Staphylococcus, Streptococcus, and Enterococcus spp. The MICs of T-3262 for 90% of strains tested were between 0.05 and 1.56 micrograms/ml. Against members of the family Enterobacteriaceae and Pseudomonas aeruginosa, the activities of T-3262 were almost equal to those of ciprofloxacin. Obligate anaerobes were also susceptible to T-3262. T-3262 was bactericidal for one strain each of Staphylococcus aureus, Escherichia coli, and P. aeruginosa at concentrations near its MIC; and fluoroquinolones, including T-3262, inhibited DNA gyrase activity at low concentrations. The 50% effective dose of T-3262 after oral administration against systemic infections with S. aureus in mice was about 6 times lower than that of ofloxacin and about 20 times lower than that of norfloxacin.     

In vitro and in vivo antibacterial efficacies of CFC-222, a new fluoroquinolone.

CFC-222 is a novel fluoroquinolone containing a C-7 bicyclic amine moiety with potent antibacterial activities against gram-positive, gram-negative, and anaerobic organisms. We compared the in vitro and in vivo activities of CFC-222 with those of ciprofloxacin, ofloxacin, and lomefloxacin. CFC-222 was more active than the other fluoroquinolones tested against gram-positive bacteria. CFC-222 was particularly active against Streptococcus pneumoniae (MIC at which 90% of isolates are inhibited [MIC90], 0.2 microg/ml), Staphylococcus aureus (MIC90, 0.2 microg/ml for ciprofloxacin-susceptible strains), and Enterococcus faecalis (MIC90, 0.39 microg/ml). Against Escherichia coli and other members of the family Enterobacteriaceae, CFC-222 was slightly less active than ciprofloxacin (MIC90s for E. coli, 0.1 and 0.025 microg/ml, respectively). The in vitro activity of CFC-222 was not influenced by inoculum size, medium composition, or the presence of horse serum. However, its activity was decreased significantly by a change in the pH of the medium from 7.0 to 6.0, as was the case for the other quinolones tested. The in vivo protective efficacy of CFC-222 by oral administration was greater than those of the other quinolones tested in a mouse model of intraperitoneally inoculated systemic infection caused by S. aureus. CFC-222 exhibited efficacy comparable to that of ciprofloxacin in the same model of infection caused by gram-negative organisms, such as E. coli and Klebsiella pneumoniae. In this infection model, CFC-222 was slightly less active than ciprofloxacin against Pseudomonas aeruginosa. These results suggest that CFC-222 may be a promising therapeutic agent in various bacterial infections.     

In vitro and in vivo antichlamydial activities of HSR-903, a new fluoroquinolone antibiotic.

The in vitro and in vivo antichlamydial activities of HSR-903 were investigated. The MICs of HSR-903 for different species of chlamydia were 0.016 to 0.063 microg/ml, which were superior to those of conventional fluoroquinolones. The therapeutic effect of HSR-903 in experimental mouse Chlamydia psittaci pneumonia was also excellent and almost equal to that of minocycline and superior to that of ofloxacin. These results indicate that HSR-903 may be useful in the treatment of respiratory infections caused by chlamydiae.     

In vitro and in vivo activities of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae.

The in vitro potency and in vivo efficacy of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae were investigated by pharmacokinetic studies with M. pneumoniae-infected hamsters. By using fluoroquinolones, macrolides, and tetracyclines as references, Q-35 was found to possess the greatest mycoplasmacidal activity. The MIC for 90% of strains tested (MIC90) and the MIC50 were 0.78 and 0.39 microgram/ml, respectively, and the MBC for 90% of strains tested (MBC90) and the MBC50 were 3.13 and 0.78 microgram/ml, respectively. The MBC50-to-MIC50 ratio for Q-35 was 2. Furthermore, only Q-35 continued to be effective against 19 strains of erythromycin-resistant mutants of M. pneumoniae. The efficacies of fluoroquinolones against M. pneumoniae were also investigated by using an experimental hamster pneumonia model to measure the CFU of M. pneumoniae in the lungs. Q-35 and ofloxacin were efficacious following oral administration of 200 mg/kg/day for 5 days, initiated 24 h after infection, while ciprofloxacin was not active. Continuous administration of Q-35 for 10 days significantly reduced numbers of viable M. pneumoniae in the lungs. These results suggest that both Q-35 and ofloxacin are effective in the early phase of infection and, moreover, that Q-35 is also effective in the middle stage of infection, when progressive lung alterations and continuous increases in mycoplasmal growth occur. Peak levels of Q-35 in sera and lungs after oral administration were higher than those of ciprofloxacin but lower than those of ofloxacin. On the basis of these results, Q-35 appears to be a promising antimicrobial agent in chemotherapy of mycoplasmal infection.     

In vitro and in vivo activities of AM-1155, a new fluoroquinolone, against Chlamydia spp.

The in vitro and in vivo activities of AM-1155, a new quinolone, against Chlamydia spp. were investigated. The MIC of AM-1155 for 10 standard strains of different Chlamydia spp. and 25 wild-type strains of Chlamydia pneumoniae isolated in Japan, which were morphologically different from clinical isolates from the United States, ranged from 0.063 to 0.125 microg/ml. Its activity was almost the same as those of sparfloxacin and tosufloxacin and was 4 and 16 times superior to those of levofloxacin and ciprofloxacin, respectively, but lower than those of clarithromycin and minocycline (range for each, 0.016 to 0.031 microg/ml). The minimal chlamydiacidal concentration of AM-1155 ranged from 0.063 to 0.125 microg/ml, while those of clarithromycin and minocycline ranged from 0.016 to 0.031 microg/ml and 0.016 to 0.063 microg/ml, respectively. The therapeutic effect of a 7-day course of AM-1155 at doses of 5 and 10 mg/kg of body weight administered orally twice daily to mice with experimental Chlamydia psittaci pneumonia was excellent, with a 100% survival rate at 21 days after infection. The efficacy was equal to those of clarithromycin and minocycline and higher than those of ciprofloxacin and ofloxacin.     

Potent antibacterial activity of Y-754, a novel benzimidazole compound with selective action against <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Y-754, a novel benzimidazole compound, was investigated for in vitro and in vivo antibacterial activity. Unlike amoxicillin, clarithromycin, and metronidazole, the compound had no activity against common aerobic and anaerobic bacteria other than Helicobacter pylori. The minimum inhibitory concentration of Y-754 against H. pylori, at 0.025µg/ml, was nearly equal to that of amoxicillin and clarithromycin. The respective concentrations of Y-754, amoxicillin, clarithromycin, and metronidazole required to inhibit 90% of 39 isolates of H. pylori were 0.05, 0.39, 6.25, and 25µg/ml, indicating the potent activity of Y-754, including activity against clarithromycin- and metronidazole-resistant strains. The anti-H. pylori activity of Y-754 was potent even at pH 5.5 and was bactericidal at concentrations of 0.1µg/ml and above. Exposure of H. pylori to Y-754 did not result in the induction of drug-resistant mutation. Oral administration (10mg/kg twice a day for 7 days) to Mongolian gerbils infected with strain ATCC 43504 demonstrated that Y-754 was effective in H. pylori eradication and that its eradication efficacy increased in line with the progress of damage to the gastric mucosa caused by H. pylori infection. Y-754 was also efficacious in the treatment of infection by the clarithromycin-resistant strain OIT-36. The results obtained lead to the expectation that the new benzimidazole Y-754 will, in the near future, be used for H. pylori eradication therapy in peptic ulcer patients.     

In vitro and in vivo antibacterial activities of DK-507k, a novel fluoroquinolone

The antibacterial activities of DK-507k, a novel quinolone, were compared with those of other quinolones: ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sitafloxacin, and garenoxacin (BMS284756). DK-507k was as active as sitafloxacin and was as active as or up to eightfold more active than gatifloxacin, moxifloxacin, and garenoxacin against Streptococcus pneumoniae, methicillin-susceptible and methicillin-resistant Staphylococcus aureus, and coagulase-negative staphylococci. DK-507k was as active as or 4-fold more active than garenoxacin and 2- to 16-fold more active than gatifloxacin and moxifloxacin against ciprofloxacin-resistant strains of S. pneumoniae, including clinical isolates and in vitro-selected mutants with known mutations. DK-507k inhibited all ciprofloxacin-resistant strains of S. pneumoniae at 1 microg/ml. A time-kill assay with S. pneumoniae showed that DK-507k was more bactericidal than gatifloxacin and moxifloxacin. The activities of DK-507k against most members of the family Enterobacteriaceae were comparable to those of ciprofloxacin and equal to or up to 32-fold higher than those of gatifloxacin, levofloxacin, moxifloxacin, and garenoxacin. DK-507k was fourfold less active than sitafloxacin and ciprofloxacin against Pseudomonas aeruginosa, while it was two to four times more potent than levofloxacin, gatifloxacin, moxifloxacin, and garenoxacin against P. aeruginosa. In vivo, intravenous treatment with DK-507k was more effective than that with gatifloxacin and moxifloxacin against systemic infections caused by S. aureus, S. pneumoniae, and P. aeruginosa in mice. In a mouse model of pneumonia due to penicillin-resistant S. pneumoniae, DK-507k administered subcutaneously showed dose-dependent efficacy and eliminated the bacteria from the lungs, whereas gatifloxacin and moxifloxacin had no significant efficacy. Oral treatment with DK-507k was slightly more effective than that with ciprofloxacin in a rat model of foreign body-associated urinary tract infection caused by a P. aeruginosa isolate for which the MIC of DK-507k was fourfold higher than that of ciprofloxacin. Oral administration of DK-507k to rats achieved higher peak concentrations in serum and higher concentrations in cumulative urine than those achieved with ciprofloxacin. These data indicate the potential advantages of DK-507k over other quinolones for the treatment of a wide range of community-acquired infections.     

In vitro and in vivo activities of DW-224a, a novel fluoroquinolone antibiotic agent

OBJECTIVES: The objective of the present study was to assess the in vitro and in vivo activities of DW-224a in order to eventually use it as an antibiotic. METHODS: DW-224a was compared with DW286, ciprofloxacin and trovafloxacin. MICs of DW-224a, DW286, ciprofloxacin and trovafloxacin were determined against several groups of clinical isolates. In addition, intraperitoneal infection was induced with various organisms in mice. Test compounds were administered once orally to mice immediately after infection. The 50% protective dose (PD50) was calculated from the survival rates on day 7 after infection. RESULTS: Against Gram-positive bacteria, the in vitro activity of DW-224a was stronger than those of ciprofloxacin and trovafloxacin, but slightly weaker than that of DW286. Against Gram-negative bacteria, the activity of DW-224a was similar to those of trovafloxacin and DW286, but weaker than that of ciprofloxacin. In experimental systemic infections in mice with various organisms, like DW286, DW-224a demonstrated potent activity against Gram-positive bacteria and somewhat less activity against Gram-negative bacteria. CONCLUSIONS: DW-224a has a broad spectrum of antimicrobial activity, which is especially potent against Gram-positive bacteria.     

In vitro and in vivo antibacterial activities of E-4868, a new fluoroquinolone with a 7-azetidin ring substituent.

E-4868, (-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-1-(2,4- difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid, is a new fluoroquinolone with an azetidine moiety at the 7 position. The in vitro activity of E-4868 has been compared with those of ciprofloxacin, ofloxacin, and fleroxacin, while the activity of ciprofloxacin was used as reference for in vivo studies. The MICs of E-4868 for 90% of the isolates tested (MIC90s) were 0.06 to 0.5 microgram/ml against gram-positive organisms, including Staphylococcus, Streptococcus, and Enterococcus spp. In general, the in vitro potency of E-4868 against gram-positive bacteria was higher than those of all of the other fluoroquinolones tested. MIC90s against members of the family Enterobacteriaceae between 0.03 and 1 microgram/ml were observed, with the exception of those against Serratia marcescens and Providencia spp., and a MIC90 of 2 micrograms/ml against Pseudomonas aeruginosa was obtained. E-4868 inhibited 90% of the Clostridium spp. and Bacteroides spp. at 2 micrograms/ml and was twofold more active than ciprofloxacin. An increase in the Mg2+ concentration from 1 to 10 mM increased the MIC between two and three times. Human urine caused a significant decrease in activity of E-4868, which was more pronounced at pH 5.5 than at pH 7.2. The presence of serum also decreased the activity of E-4868. Fifty percent effective dose (ED50) values against experimental Escherichia coli HM-42 infections in mice were 3.9 mg/kg of body weight with E-4868 and 3.5 mg/kg of body weight with ciprofloxacin. Corresponding ED50 values against P. aeruginosa HS-116 were 93.2 and 107.8 mg/kg, respectively, and those against Staphylococcus aureus HS-93 were 6.5 and 44.6 mg/kg, respectively. In experimental infections with Streptococcus pneumoniae 84551, the ED50 value of E-4868 was 154.4 mg/kg, while ciprofloxacin proved totally inactive at a dose of 400 mg/kg. When E-4868 was administered orally at a dose of 50 mg/kg in mice, the area under the concentration-time curve (0 to 4 h) value was 28.4 microgram . h/ml, while an area under the concentration-time curve value of 2.3 microgram . h/ml was observed for ciprofloxacin at the same dose. In these studies, levels of the two agents in blood 1 h postadministration were 7.6 and 1.2 microgram/ml, respectively.     

In vitro and in vivo antibacterial activities of E-4497, a new 3-amine-3-methyl-azetidinyl tricyclic fluoroquinolone.

The in vitro and in vivo antibacterial activities of a new tricyclic fluoroquinolone, E-4497 [S(-)-9-fluoro-3-methyl-10-(3-amine-3-methyl-azetidin-1-yl)-7-oxo- 2,3-dihydro- 7H-pyrido-(1,2,3-de)-1,4-benzoxazine-6-carboxylic acid], were evaluated in comparison with those of DR-3355 [S-(-)-ofloxacin], norfloxacin, and ciprofloxacin. E-4497 was more potent than norfloxacin and as potent as or more potent than DR-3355 and ciprofloxacin against Staphylococcus spp., Streptococcus spp., and Enterococcus faecalis. With the exception of Providencia spp., E-4497 inhibited 90% of the Enterobacteriaceae at less than or equal to 0.25 micrograms/ml. Against enteric bacteria, E-4497 was similar in potency to norfloxacin but less potent than DR-3355 and ciprofloxacin. For Pseudomonas aeruginosa, the MICs of E-4497, DR-3355, norfloxacin, and ciprofloxacin for 90% of strains were 2, 2, 4, and 0.5 micrograms/ml, respectively. Against Clostridium perfringens and Bacteroides fragilis, E-4497 (MICs for 90% of strains, 2 and 8 micrograms/ml, respectively) was two- to fourfold more active than norfloxacin and ciprofloxacin. E-4497 activity decreased moderately in the presence of 10 mM Mg2+. Urine at pH 5.5 caused a significant decrease in activity compared with urine at pH 7.2. However, the presence of serum either had no effect or increased the activity of E-4497. In general, E-4497 was bactericidal at the MIC. In systemic infections with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa in mice, the protective effect of E-4497 was generally greater than that of norfloxacin and comparable to those of DR-3355 and ciprofloxacin.     

In vitro and in vivo activity of NY-198, a new difluorinated quinolone.

NY-198 [1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid hydrochloride] is a new difluorinated quinolone characterized by the presence of a C-methyl group at the 3 position of the piperazine moiety. It has a broad antibacterial spectrum. The in vitro antibacterial activity of NY-198 was almost the same as those of ofloxacin and norfloxacin, but far exceeded that of pipemidic acid. NY-198 was more active than norfloxacin against Pseudomonas maltophilia, Acinetobacter calcoaceticus, and anaerobic microorganisms. Cross resistance was not observed between NY-198 and various antibiotics including methicillin, gentamicin, and ampicillin. NY-198 had bactericidal activity at the MIC or slightly higher than the MIC. It showed excellent antibacterial activity against various systemic infections in mice. After oral administration, NY-198 was two times more active than or as active as ofloxacin and two to four times more active than norfloxacin.     

In vitro and in vivo activity of DL-8280, a new oxazine derivative.

DL-8280, 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido-(1,2,3-de)1,4-benzoxazine-6-carboxylic acid, is a new nalidixic acid analog with a broad spectrum of antibacterial activity against gram-negative and gram-positive bacteria, including obligate anaerobes. The activity of DL-8280 against Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, and Clostridium perfringens was roughly comparable to that of norfloxacin and far exceeded that of pipemidic acid and nalidixic acid. DL-8280 had greater activity against Staphylococcus spp., Streptococcus spp., Pseudomonas maltophilia, Acinetobacter spp., and Bacteroides fragilis than did norfloxacin, pipemidic acid, and nalidixic acid. Nalidixic acid-resistant Enterobacteriaceae, ampicillin-resistant gonococci, and clindamycin-resistant obligate anaerobes were also susceptible to DL-8280. The activity of DL-8280 was affected very little by inoculum size, and its action was bactericidal at two times the minimal inhibitory concentrations at most. Administered orally to mice experimentally infected with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Proteus mirabilis, Serratia marcescens, or P. aeruginosa, DL-8280 was 2 to 7 times more effective than norfloxacin and 7 to more than 50 times more active than pipemidic acid.     

In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic

The in vitro activity of LY 146032, a cyclic lipopeptide antibiotic belonging to the class of agents designated A21978C, was compared with those of vancomycin, cefpirome, cefotaxime, and clindamycin against selected gram-positive bacteria. The new drug inhibited all staphylococcal isolates, including methicillin-resistant strains, at concentrations of less than or equal to 1.0 microgram/ml. The activity of LY 146032 was comparable to that of vancomycin against most streptococci, but the latter demonstrated greater potency against Streptococcus faecium and penicillin-resistant strains of pneumococci and viridans group streptococci. LY 146032 was markedly less active than vancomycin against Listeria monocytogenes (MICs for 90% of strains tested, 16 and 1.0 microgram/ml, respectively). The activity of LY 146032 was enhanced as the concentration of calcium in the test medium was increased. MBCs were within eightfold of the MIC for each of 12 strains tested. In a rat model of enterococcal endocarditis, the administration of LY 146032 resulted in increased survival and a reduction in the bacterial titer within cardiac vegetations compared with untreated control animals.     

In-vitro activity of sitafloxacin (DU-6859a), either singly or in combination with rifampin analogs, against Mycobacterium leprae

 The in-vitro antibacterial activity of sitafloxacin (DU-6859a) against Mycobacterium leprae was evaluated and compared with those of ofloxacin, levofloxacin, and ciprofloxacin. Two biochemical indicators (intracellular ATP and uptake of [³H]-thymidine) were used to measure the in-vitro growth of M. leprae in Dhople-Hanks (DH) medium. Sitafloxacin was found to be more potent than the other three commonly used fluoroquinolones, with the minimum inhibitory concentration (MIC) against M. leprae being 0.1875 μg/ml and the action being bactericidal. The MICs of ofloxacin, levofloxacin, and ciprofloxacin were 1.5, 0.75, and 3.0 μg/ml, respectively. Similar to ofloxacin and levofloxacin, sitafloxacin also exhibited synergistic activity when combined with either rifabutin or KRM-1648, but not with rifampin. Thus, further studies on the incorporation of sitafloxacin in multidrug therapy regimens in treating leprosy patients are suggested. Received: July 30, 2002 / Accepted: October 9, 2002 Acknowledgments The authors wish to thank Daiichi Pharmaceutical Company, Ltd. for supplying sitafloxacin for this study.