In vitro activity of levofloxacin against coagulase-positive and -negative staphylococci.

The in vitro activity of levofloxacin compared with that of ciprofloxacin, ofloxacin and norfloxacin were examined by conventional in vitro tests against 150 clinical isolates of staphylococci, subdivided according to species and susceptibility to methicillin. Although the minimum inhibitory concentrations (MICs) of all quinolones were highest in methicillin-resistant Staphylococcus aureus strains, the activity of levofloxacin was almost complete in methicillin-resistant S. epidermidis and methicillin-resistant S. haemolyticus when compared with ciprofloxacin and ofloxacin, which showed more than 30% resistance. Methicillin-susceptible S. aureus and S. epidermidis strains were susceptible to all quinolones with few differences between the antibiotics tested. The minimal bactericidal activity of levofloxacin was within the double dilution range of MIC values for all strains tested, demonstrating its potent role against staphylococci. In time-kill studies, levofloxacin exerted bactericidal activity within 3 h against all staphylococci. These in vitro results suggest that levofloxacin is a potent fluoroquinolone against coagulase-negative staphylococci and that it is both methicillin-susceptible and resistant. Further studies are necessary to determine the role of this drug in the treatment of infections sustained by these microorganisms.     

In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.     

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).     

Synthesis and in-vitro antibacterial activity of 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives

A series of novel 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives was designed, synthesized and characterized by (1)H-NMR, MS and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds display rather weak potency against the tested Gram-negative strains, but most of them exhibit good potency in inhibiting the growth of S. aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis including methicillin-resistant S. epidermidis (MRSE) (MIC: 0.125-8 μg/mL). In particular, the compound 9g is 2 to 32 fold more potent than gemifloxacin (GM), moxifloxacin (MX), gatifloxacin (GT), and levofloxacin (LV) against S. pneumoniae 08-3, K. pneumoniae 09-23, and P. aeruginosa ATCC27853, 4 to 32 fold more potent than MX, GM, and LV against K. pneumoniae 09-21, and more active than or comparable to the four reference drugs against P. aeruginosa 09-32.     

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.     

Selection of resistant variants of respiratory pathogens by quinolones.

Quinolones are widely used in the treatment of respiratory tract infections. However, some disquiet has been expressed over using quinolones for community-acquired pneumonia since their activity is generally rather poor against Streptococcus pneumoniae. In addition, it is known that resistant variants emerge at a fairly high frequency during exposure of Enterobacteriaceae to quinolones; if this also occurred during quinolone treatment of community-acquired pneumonia it could lead to an increased risk of clinical failure. We therefore determined the selection rate of quinolone-resistant variants for six strains of S. pneumoniae, Haemophilus influenzae and Moraxella catarrhalis with nalidixic acid (except for S. pneumoniae), ciprofloxacin, ofloxacin and levofloxacin. We were only able to select resistant variants at low frequency from two of the six strains of S. pneumoniae with ciprofloxacin: no resistant variants were selected by either ofloxacin or levofloxacin. Variants of H. influenzae and M. catarrhalis with decreased susceptibility to quinolones were produced both with more strains and with a greater frequency; however, these variants still remained susceptible according to the NCCLS guidelines. Our study suggests that resistant variants of S. pneumoniae are relatively unlikely to occur in individuals treated with fluoroquinolones especially if they are given quinolones with enhanced anti-gram-positive activity compared to ciprofloxacin.     

Antimicrobial resistance and production of biofilms in clinical isolates of coagulase-negative Staphylococcus strains

Coagulase-negative Staphylococcus (CNS) strains are frequently associated with bacteremia and hospital-acquired infections. 293 CNS strains were isolated from 744 samples from a dialysis center in S. M. de Tucumán, Argentina, from hemocultures, catheters and urine and identified as S. epidermidis, S. haemolyticus, S. saprophyticus, S. hominis and S. cohnii. 13 antibiotics were tested for antibacterial resistance. 75% of S. saprophyticus, 66% of S. epidermidis and 57% of S. haemolyticus was resistant to erythromycin and 50% of S. haemolyticus was resistant to ciprofloxacin. OXA resistance was found in 43% of S. haemolyticus. Presence of PBP 2a in OXA-R strains was confirmed with the modified agglutination assay (MRSA) and presence of the mecA gene. 15 strains with intermediate halos for vancomycin and teicoplanin showed a MIC in solid and liquid medium 相似文献   

In vitro activity of sitafloxacin compared with several fluoroquinolones against Streptococcus anginosus and Streptococcus constellatus

The in vitro activities of sitafloxacin and seven other fluoroquinolones a (ciprofloxacin, tosufloxacin, sparfloxacin, levofloxacin, T-3811ME, moxifloxacin and trovafloxacin) were examined by the microdilution method against 79 clinically isolated 'Streptococcus milleri' group (SMG) microorganisms. No statistically significant differences were found between the minimum inhibitory concentrations (MIC(50) and MIC(90)) against Streptococcus anginosus and Streptococcus constellatus. Sitafloxacin was the most active agent of the eight fluoroquinolones tested against SMG, with a MIC(90) of 0.06 microg/mL, which was 8 times more active than ciprofloxacin and 16 times more active than levofloxacin. Although none of the SMG strains showed high resistance to any of the fluoroquinolones tested, three agents (trovafloxacin, sitafloxacin and T-3811ME) had low MICs against 23 SMG strains against which levofloxacin had a MIC> 1 microg/mL. In conclusion, several fluoroquinolones have low MICs against SMG, but sitafloxacin has the lowest.     

Comparative in vitro activity of gemifloxacin to other fluoroquinolones and non-quinolone agents against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in the United States in 1999-2000

This study was undertaken to assess the in vitro activity of gemifloxacin, five other fluoroquinolone antimicrobial agents (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin and ofloxacin) and other non-quinolone comparator agents (ampicillin, erythromycin, clindamycin, doxycycline, penicillin and trimethoprim/sulphamethoxazole) against Streptococcus pneumoniae collected in the United States. Susceptibility testing of 550 S. pneumoniae, 290 Haemophilus influenzae and 205 Moraxella catarrhalis showed that 38.2% of pneumococci were penicillin nonsusceptible, while 26.2 and 95.6% of H. influenzae and M. catarrhalis, respectively, produced beta-lactamase. Overall new fluoroquinolones were the most active agents. The in vitro activity (based on MIC90 in mg/l) of the six fluoroquinolones was gemifloxacin>moxifloxacin>gatifloxacin>levofloxacin>ciprofloxacin and ofloxacin.     

Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms

Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens. Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms. We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms. Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae. Ciprofloxacin and levofloxacin were active but less potent. All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa. Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.     

六种氟喹诺酮对肠球菌的体外抗菌活性及利血平的影响

目的：研究氟喹诺酮类抗菌药物对临床分离肠球菌的体外抗菌活性,以及多重耐药泵抑制剂利血平对抗菌活性的影响.方法：收集临床分离的101株肠球菌（66株粪肠球菌和35株屎肠球菌）,用琼脂稀释法测定应用利血平前后6种氟喹诺酮对菌株的最低抑菌浓度（MIC）.结果：诺氟沙星、环丙沙星、氧氟沙星、左氧氟沙星、加替沙星、莫西沙星对66株粪肠球菌的MIC90依次为256、64、64、16、16、8 mg/L,对35株屎肠球菌的MIC90依次为＞512、512、128、128、32、32 mg/L.应用利血平之后,上述6种药物对粪肠球菌抗菌活性提高（MIC下降2倍或2倍以上）的株数依次为66（100%）、54（81.8%）、4（6.1%）、4（6.1%）、32（48.5%）和3（4.5%）株,对屎肠球菌抗菌活性提高的株数依次为35（100%）、29（82.9%）、1（2.9%）、0（0%）、6（20.7%）和2（5.7%）株.结论：新氟喹诺酮加替沙星、莫西沙星增强了对肠球菌的抗菌活性,利血平能够提高全部或部分被检测肠球菌对诺氟沙星、环丙沙星和加替沙星的敏感性,但仅使少数被检测肠球菌对氧氟沙星、左氧氟沙星和莫西沙星的敏感性提高.     

Du6859a及其他新的氟喹诺酮类药物的体外抗菌活性

用琼脂稀释法测定Ｄｕ６８５９ａ对１２０６株临床分离菌的抗菌作用，并与其同类品种（司帕沙星、托舒沙星、诺氟沙星、氧氟沙星、左氟沙星、环丙沙星）比较。Ｄｕ６８５ｑａ对金葡球菌不产酶株、ＭＳＳＡ、ＭＲＳＡ、ＭＲＳＥ，溶血性链球菌和肺炎球菌的ＭＩＣ＿（９０）均为０．５ｍｇ／Ｌ；对肠球菌的ＭＩＣ＿（９０）为２ｍｇ／Ｌ，优于其同类品种。多数肠杆菌科细菌可为０．２５ｍｇ／Ｌ，铜绿假单胞菌可为０．５ｍｇ／Ｌ的本品所抑制，其抗菌活性与司帕沙星和托舒沙星相似。Ｄｕ６８５９ａ对各种厌氧菌亦具良好作用，多数菌株可为０．５ｍｇ／Ｌ的浓度抑制。因此认为本品具有良好的临床应用前景，值得进一步临床试验。     

The fluoroquinolones exert a reduced rate of kill against Enterococcus faecalis.

The bactericidal activities of ciprofloxacin, ofloxacin and DR-3355 have been investigated against Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis over 24 h. The three fluoroquinolones were found to be rapidly bactericidal against the staphylococci, killing over 99% of the bacteria during the first 3 h of exposure with a further reduction in viability of approximately one logarithm occurring over the next 21 h. In contrast, the fluoroquinolones displayed a much slower rate of kill against E. faecalis, as little or no bactericidal activity was detected over the first 3 h for both E. faecalis ATCC19433 and a clinical isolate. At 6 h all three of the drugs were bactericidal against the enterococci although the amount of kill was not as great as against the staphylococci. However, at 24 h the amount of kill obtained with all three drugs was similar to that obtained for staphylococci exposed to these drugs. Ciprofloxacin, ofloxacin and DR-3355 were not active against E. faecalis ATCC19433 in phosphate buffered saline and therefore require cell division for their bactericidal activity against this species.     

加替沙星对金黄色葡萄球菌的体外抗菌活性

考察加替沙星对金黄色葡萄球菌的体外抗菌活性以及抗MRSA的能力。采用药敏纸片法（K－B法），从129株临床分离的金黄色葡萄球菌筛选对甲氧西林和氟喹诺酮类药物的耐药菌株，用琼脂二倍稀释法对交叉耐药菌进行MIC测试，比较了加替沙星与环丙沙星等第二代氟喹诺酮类药物的耐药菌株，用琼脂二倍稀释法对交叉耐药菌进行MIC测试，比较了加替沙星与环丙沙星等第二代氟喹诺酮类药物的抗菌活性。用苯唑西林筛选三代自发突变株，比较环丙沙星、加替沙星对MRSA的抗菌活性。实验表明，苯唑西林、环丙沙星、氧氟沙星、左氧氟沙星对129株金黄色葡萄球菌的耐药率相似。体外活性表明，加替沙星比环丙沙星等第二代氟喹诺酮类药物的抗菌活性强，抗MRSA菌株的活性较强；敏感金黄色葡萄球菌发生加替沙星耐药的突变频率在所试药物中也是最低的。说明加替沙星比环丙沙星等第二代氟喹诺酮类药物的抗菌活性得到明显提高。     

In vitro activity of clinafloxacin against fluoroquinolone resistant Spanish clinical isolates.

The in vitro activity of clinafloxacin against 162 ciprofloxacin-resistant clinical isolates was determined. Isolates were selected when their MIC to ciprofloxacin was 2 mg/l (intermediate) or > 2 mg/l (resistant). The following strains were tested: 61 Escherichia coli, 12 Klebsiella pneumoniae, 7 Proteus mirabilis, 21 Serratia marcescens, 4 Enterobacter cloacae, 21 Pseudomonas aeruginosa, 21 Staphylococcus. aureus (resistant to methicillin) and 15 Enterococcus spp. Clinafloxacin, ciprofloxacin, ofloxacin and norfloxacin activities were evaluated by agar dilution using Müeller-Hinton agar according to NCCLS recommendations. Of the 162 isolates, 16 (9.8%) were intermediate and 146 (90.1%) resistant to ciprofloxacin. 95 of the 162 strains (58.6%) were susceptible, 27 (16.7%) intermediately susceptible, and 40 strains (24.7%) were resistant to clinafloxacin. The percentage susceptible to clinafloxacin was 65.6% for E. coli, 75% for K. pneumoniae, 71.4% for P. mirabilis, 28.6% for S. marcescens, 75% for E. cloacae, 33.3% for P. aeruginosa, 90.5% for S. aureus and 40% for Enterococcus spp. Clinafloxacin was active against 58.6% of the ciprofloxacin-resistant clinical isolates tested. It was particularly active against S. aureus strains resistant to both ciprofloxacin and methicillin.     

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。     

司帕沙星与其他5种抗菌药体外抗菌活性比较研究

测定了司帕沙星对临床分离的１９９ 株致病菌的体外抗菌活性并与氧氟沙星、环丙沙星、头孢唑啉、头孢噻肟、阿米卡星的抗菌活性进行比较。司帕沙星对革兰阳性菌的ＭＩＣ９０为０．１２５～０．５ｍ ｇ／Ｌ,对金葡球菌、化脓链球菌的抑菌率均为１００％ ,强于氧氟沙星、环丙沙星;对革兰阴性菌也具有良好的体外抗菌活性,与氧氟沙星、环丙沙星相似。不同细菌接种量和不同浓度血清对其抗菌活性无明显影响,仅在ｐＨ５．０ 时抗菌活性略有下降     

妥舒沙星的体内外抗菌作用研究

测定妥舒沙星的体内外抗菌活性。以同类氟喹诺酮类及其他抗菌药物为对照,测定了６８９株临床分离菌对药物的敏感性,结果显示,妥舒沙星对需氧革兰氏阳性球菌（除ＭＲＳＡ外）均有良好的抗菌作用,对金葡球菌、肺炎球菌和溶血性链球菌的抗菌活性高;妥舒沙星对需氧革兰氏阴性菌具强大的抗菌作用,对肠杆菌科细菌、流感杆菌和淋球菌的抗菌作用尤强;妥舒沙星对脆弱拟杆菌等厌氧菌亦具良好抗菌作用。妥舒沙星对需氧革兰氏阳性球菌及厌氧菌的作用明显优于环丙沙星、氧氟沙星和诺氟沙星,对需氧革兰氏阴性杆菌的作用与其他受试氟喹诺酮类相仿。妥舒沙星对小鼠实验性细菌感染具有明显保护作用,口服或静注妥舒沙星对金葡球菌的体内抗菌作用明显优于环丙沙星;对大肠埃希氏菌的抗菌作用优于或与环丙沙星相似;对铜绿假单胞菌的作用与环丙沙星相似。     

6种氟喹诺酮类药物对临床分离金葡萄的抗菌活性比较

目的：观察临床分离金葡萄对6种氟喹诺酮类药物的耐药情况。方法：用琼脂稀释法测定诺氟沙星（NFLX）、氧氟沙星（OFLX）、氟罗沙星（FLRX）、环丙沙星（CPFX）、司帕沙星（SPFX）、托舒沙星（TFLX）6种2、3代氟喹诺桐类药物对成都地区155株临床分离金葡菌的体外抗菌活性。结果：金葡菌对6种药物的耐药率分别为诺氟沙星35.5%。氟罗沙星34.19%,环丙沙星27.75%,托舒沙星27.75% ,氧氟沙星25.81%,司帕沙星25.81%。结论：氟喹诺酮类药物的广泛应用已使细菌的耐药性明显增高,各药MIC90均超过16mg.L^-1,比以往文献报道的本地区金葡萄耐药性明显升高,提示要合理应用氟喹诺酮类药物,减少耐药菌株的增加。     

最新凝固酶阴性葡萄球菌耐药及流行变迁情况分析

通过对天津市１９９１￣１９９２年间的８４株凝固酶阴性葡萄球菌（ＣＮＳ）和１９９６￣１９９８年３月间的１０５株ＣＮＳ的比较研究发现，表皮葡萄球菌的分离率仍居首位，溶血葡萄球菌和模仿葡萄球菌所占的比例有所提高。从耐药性的比较发现，对环丙氟哌酸和红霉素的耐药率有显著增加。