In vitro activities of ramoplanin and four glycopeptide antibiotics against clinical isolates of Clostridium difficile.

Seventy strains of Clostridium difficile, all isolated from symptomatic patients, were found to be uniformly susceptible to ramoplanin, a new glycolipodepsipeptide antibiotic, and to four glycopeptides (vancomycin, teicoplanin, and two semisynthetic teicoplanin derivatives). Ramoplanin is recommended for further evaluation in the treatment of C. difficile-associated disease.     

In vitro activity of sparfloxacin and six reference antibiotics against gram-positive bacteria.

The in vitro activity of sparfloxacin, a new fluoroquinolone, was assessed against 234 gram-positive bacterial isolates by agar dilution (10(4) CFU/spot). Sparfloxacin activity was compared with that of ciprofloxacin and five other antibiotics. Sparfloxacin was the most active drug tested against methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (MIC90, 0.125-0.25 mg/l). Sparfloxacin was also the most active drug tested against Enterococcus faecalis (MIC90, 1 mg/l) and showed equal activity against gentamicin-susceptible and gentamicin-resistant (MIC greater than 2,000 mg/l) enterococci. Sparfloxacin was the most active quinolone tested against Streptococcus pneumoniae and S. pyogenes (MIC90, 1 mg/l). Most Corynebacterium jeikeium showed exquisite susceptibility to sparfloxacin (MIC, 0.06-0.25 mg/l). For MRSA, time-kill curves showed sparfloxacin to be rapidly bactericidal at the MIC of the organism. Sparfloxacin showed greater and more sustained bactericidal activity than ciprofloxacin and vancomycin at 1x and 2x the MIC. Reduction in the activity of sparfloxacin occurred with decreased agar pH (from 7.0 to 6.0) and increased bacterial inoculum. Sparfloxacin showed superior activity compared to reference drugs against most gram-positive bacteria.     

In vitro activities and targets of three cephem antibiotics against Haemophilus influenzae.

The antimicrobial activities of cefixime, cefpodoxime, and ceftibuten were determined with 18 ampicillin-susceptible (Amps), 13 ampicillin-resistant beta-lactamase-producing (AmprBLP), and 7 ampicillin-resistant non-beta-lactamase-producing (AmprNBLP) strains of Haemophilus influenzae. An effect of inoculum density on apparent MIC, the bactericidal activity of these agents, and the targets of the three cephems were determined. The MICs of cefixime, cefpodoxime, and ceftibuten for 90% of the Amps and AmprBLP isolates were 0.04, 0.08, and 0.08 microgram/ml, respectively. In contrast, the MICs for 90% of the AmprNBLP strains were 0.96, 1.92, and 7.68 micrograms/ml. No significant inoculum effect was observed for any group of strains comparing inocula of 10(3) and 10(5) CFU, whereas only the AmprNBLP isolates showed a marked effect at an inoculum of 10(6) CFU. Although bactericidal levels were achieved for the Amps and AmprBLP strains, tolerance to cefixime and ceftibuten was observed. The bactericidal activity for the AmprNBLP strains was limited, with cefixime showing the highest activity of the three cephems. Penicillin-binding proteins 2, 4, and 5 revealed high affinity, with 50% inhibitory concentration levels below the MIC for all three cephems, suggesting that these are important targets of these agents in H. influenzae. We conclude that the cephems are highly active in vitro against Amps and AmprBLP strains of H. influenzae, but less so against AmprNBLP isolates.     

In vitro activities of new beta-lactam antibiotics against Acinetobacter spp

The in vitro activities of new beta-lactam antibiotics was studied and compared with those of other known agents against 51 clinical isolates of Acinetobacter calcoaceticus subsp. anitratus and 23 isolates of A. calcoaceticus subsp. lwoffi. Of the new beta-lactam antibiotics, imipemide (N-formimidoyl thienamycin), ceftazidime, ceftizoxime, ceftriaxone, and piperacillin demonstrated good activities. The minimal inhibitory concentrations for A. calcoaceticus subsp. lwoffi were lower than those obtained for A. calcoaceticus subsp. anitratus.     

In vitro activities of trovafloxacin against 557 strains of anaerobic bacteria.

The antimicrobial activity of trovafloxacin for 557 strains of anaerobic bacteria was determined by the National Committee for Clinical Laboratory Standards-approved Wadsworth agar dilution technique. The species tested included Bacteroides fragilis (n = 91), other members of the B. fragilis group (n = 130), Campylobacter gracilis (n = 15), other Bacteroides spp. (n = 16), Prevotella spp. (n = 49), Porphyromonas spp. (n = 15), Fusobacterium spp. (n = 62), Bilophila wadsworthia (n = 24), Sutterella wadsworthensis (n = 21), Clostridium spp. (n = 61), Peptostreptococcus spp. (n = 38), and gram-positive non-spore-forming rods (n = 35). Trovafloxacin inhibited all strains of B. fragilis at < or = 0.5 microgram/ml, 99% of other B. fragilis group species at < or = 2 micrograms/ml, and 96% of all anaerobes tested at < or = 2 micrograms/ml.     

In vitro activities of several new macrolide antibiotics against Mycobacterium avium complex.

The in vitro activities of 12 macrolide compounds against 28 Mycobacterium avium complex strains isolated from patients with acquired immunodeficiency syndrome were determined by the conventional proportion method and by the BACTEC method. Clarithromycin (A-56268; TE-031), a new macrolide compound, was the most active agent tested, inhibiting 90% of strains at an MIC of 4 micrograms/ml by the BACTEC method. Roxithromycin (RU 28965) and erythromycylamine inhibited 90% of strains at 16 micrograms/ml. The organisms showed high levels of resistance to most other macrolide compounds.     

西他沙星的体外抗菌作用研究

目的评价西他沙星的体外抗菌作用。方法采用琼脂对倍稀释法测定西他沙星对503株临床分离菌的体外抗菌活性,并与有关抗菌药进行比较。结果西他沙星对肺炎链球菌、化脓性链球菌、B群链球菌的MIC50为0.12 mg/L,对MSSA的MIC50为0.06 mg/L,对MSCNS的MIC50为0.03 mg/L,对MRSA的MIC50为1 mg/L,对MRCNS的MIC50为0.06 mg/L。本品对流感嗜血杆菌、卡他莫拉菌、非产ESBLs肺炎克雷伯菌的MIC50为≤0.03 mg/L,对产ESBLs肺炎克雷伯菌的MIC50为0.25 mg/L,对非产ESBLs大肠埃希菌的MIC50为1 mg/L,对产ESBLs大肠埃希菌的MIC50为2 mg/L;对易产诱导酶的阴沟肠杆菌、产气肠杆菌、枸橼酸杆菌、黏质沙雷菌的MIC50为≤0.03～0.125 mg/L,对洋葱伯克霍尔德菌的MIC50为0.25 mg/L,对铜绿假单胞和嗜麦芽窄食单胞菌为0.5 mg/L,对鲍曼不动杆菌和木糖氧化无色杆菌为1 mg/L。培养基pH值的改变、细菌接种量、血清含量改变对该药抗菌活性无明显影响。结论西他沙星具有良好广谱抗菌作用,值得进一步进行临床研究。     

利奈唑胺的体外抗菌作用研究

目的评价抗菌新药利奈唑胺的体外抗菌作用。方法采用琼脂对倍稀释法测定利奈唑胺对579株临床分离菌的体外抗菌活性，并与有关抗菌药进行比较；测定利奈唑胺的杀菌浓度和杀菌曲线；培养条件对利奈唑胺抗菌活性的影响。结果利奈唑胺对葡萄球菌属、肺炎链球菌等链球菌属、肠球菌属临床分离菌均具高度抗菌活性，包括对其中的甲氧西林耐药葡萄球菌、青霉素中介肺炎链球菌亦具良好的抗菌作用。对流感嗜血杆菌、淋病奈瑟菌的抗菌活性较低。对脆弱拟杆菌等厌氧菌具较高抗菌活性。利奈唑胺对耐药的革兰阳性球菌的抗菌作用与万古霉素和替考拉宁相仿或略强。最低杀菌浓度（MBC）测定及杀菌曲线试验结果显示利奈唑胺对肺炎链球菌、溶血性链球菌具有很强的杀菌作用，对大部分葡萄球菌属具杀菌作用，对肠球菌仅具抑菌作用。培养基pH值的改变、细菌接种量的改变对利奈唑胺抗菌活性有一定影响，人血清含量改变对该药抗菌活性无明显影响。结论利奈唑胺对需氧革兰阳性球菌，包括多重耐药菌具有高度抗菌活性，且与其他抗菌药问无交叉耐药。提示利奈唑胺对革兰阳性球菌，尤其是多重耐药株所致感染的控制将具有重要作用。     

头孢西酮的体外抗菌活性

目的 评价头孢西酮的体外抗菌活性.方法 采用琼脂对倍稀释法测定头孢西酮对568株临床分离菌的体外抗菌活性,并与相关抗菌药进行比较;测定头孢西酮的杀菌浓度和杀菌曲线以及培养条件对头孢西酮抗菌活性的影响.结果 在需氧革兰阳性菌中,头孢西酮对甲氧西林敏感金葡菌(MSSA)和甲氧西林敏感凝同酶阴性葡萄球菌(MSCNS)、青霉素敏感肺炎链球菌(PSSP)以及β溶血性链球菌均有很好的抗菌活性,MIC90≤1 mg/L.头孢西酮对流感嗜血杆菌和卡他莫拉菌的MIC90为8 mg/L.在革兰阴性菌中,头孢西酮对非产ESBLs的肺炎克雷伯菌、大肠埃希菌和奇异变形杆菌仍保持很好的抗菌活性.头孢西酮对产ESBLs的肺炎克雷伯菌、大肠埃希菌、摩根摩根菌、沙雷菌、阴沟肠杆菌和不发酵糖革兰阴性菌中铜绿假单胞菌、不动杆菌属均无抗菌活性.培养基pH值的改变、细菌接种量、血清含量改变对该药抗菌活性无明显影响.结论 头孢西酮对社区感染常见病原菌均有较好的抗菌活性.     

In vitro antimicrobial activity against reference strains and field isolates of Treponema hyodysenteriae.

The in vitro susceptibilities of eight isolates of Treponema hyodysenteriae from pigs naturally infected with swine dysentery between 1976 and 1983 were determined by an agar dilution technique. Carbadox, olaquindox, tiamulin, metronidazole, furazolidone, and monensin were the most active against these field isolates regardless of the year of recovery. The influence of inoculum size on the MICs against four reference strains of T. hyodysenteriae was studied. Various degrees of activities of ampicillin and lincomycin were found, depending on the inoculum size. The effect of successive in vitro subcultures on the susceptibility of a reference strain of T. hyodysenteriae was examined. The strain resistant to tylosin became susceptible to the drug.     

In vitro activity of AT-4140 against clinical bacterial isolates.

The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.     

In vitro activities of azithromycin, clarithromycin, and other antibiotics against Chlamydia pneumoniae.

The in vitro susceptibilities of Chlamydia pneumoniae isolates to macrolide, tetracycline, and quinolone antibiotics were determined. Tetracycline, clarithromycin, and erythromycin had the lowest MICs in the first cell culture passage. Azithromycin required the lowest concentration for complete inhibition of inclusion formation on the second pass into antibiotic-free medium, likely reflecting its high intracellular concentrations.     

In vitro antibacterial activities of antibiotics against Pseudomonas aeruginosa in peritoneal dialysis fluid.

Intraperitoneal antibiotics are used to treat Pseudomonas aeruginosa peritonitis, a serious complication of continuous ambulatory peritoneal dialysis. However, P. aeruginosa killing is often inefficient despite low MBCs. Broth dilution MIC/MBC and time kill curves of tobramycin, amikacin, netilmicin, azlocillin, piperacillin, ceftazidime, cefsulodin, and ciprofloxacin were determined in peritoneal dialysis fluid (PDF), buffered PDF, fluid recovered from patients on continuous ambulatory peritoneal dialysis (RPF), and cation-supplemented Mueller-Hinton broth. MBCs of all antibiotics were 8 to 16 times greater in PDF and RPF than in Mueller-Hinton broth or buffered PDF. Use of the time kill curve technique and Mueller-Hinton broth showed that aminoglycosides killed greater than or equal to 99.9% of P. aeruginosa at 1 h, ciprofloxacin killed greater than or equal to 99.9% at 2 h, and beta-lactams killed greater than or equal to 99.9% at 6 h. In contrast, killing was not demonstrated in PDF by any drug at 6 h and by aminoglycosides only at 24 h. Bactericidal activity was optimal in RPF for ciprofloxacin at 1 h and for aminoglycosides at 2 h; bactericidal activity was not demonstrated in RPF with any beta-lactam (no kill by penicillins; less than 99% kill by cephalosporins). Slow bacterial growth, increased protein binding, and glucose concentrations and other inhibitors may interfere with beta-lactam activity in RPF. These considerations and reported clinical failures and toxicity of aminoglycoside therapy warrant further study of quinolones and drug combinations in P. aeruginosa peritonitis.     

In vitro activities of faropenem against 579 strains of anaerobic bacteria

The activity of faropenem, a new oral penem, was tested against 579 strains of anaerobic bacteria by using the NCCLS-approved reference method. Drugs tested included amoxicillin-clavulanate, cefoxitin, clindamycin, faropenem, imipenem, and metronidazole. Of the 176 strains of Bacteroides fragilis group isolates tested, two isolates had faropenem MICs of 64 micro g/ml and imipenem MICs of >32 micro g/ml. Faropenem had an MIC of 16 micro g/ml for an additional isolate of B. fragilis; this strain was sensitive to imipenem (MIC of 1 micro g/ml). Both faropenem and imipenem had MICs of < or=4 micro g/ml for all isolates of Bacteroides capillosus (10 isolates), Bacteroides splanchnicus (13 isolates), Bacteroides ureolyticus (11 isolates), Bilophila wadsworthia (11 isolates), Porphyromonas species (42 isolates), Prevotella species (78 isolates), Campylobacter species (25 isolates), Sutterella wadsworthensis (11 isolates), Fusobacterium nucleatum (19 isolates), Fusobacterium mortiferum/varium (20 isolates), and other Fusobacterium species (9 isolates). Faropenem and imipenem had MICs of 16 to 32 micro g/ml for two strains of Clostridium difficile; the MICs for all other strains of Clostridium tested (69 isolates) were < or =4 micro g/ml. Faropenem had MICs of 8 and 16 micro g/ml, respectively, for two strains of Peptostreptococcus anaerobius (MICs of imipenem were 2 micro g/ml). MICs were < or =4 micro g/ml for all other strains of gram-positive anaerobic cocci (53 isolates) and non-spore-forming gram-positive rods (28 isolates). Other results were as expected and reported in previous studies. No metronidazole resistance was seen in gram-negative anaerobes other than S. wadsworthensis (18% resistant); 63% of gram-positive non-spore-forming rods were resistant. Some degree of clindamycin resistance was seen in most of the groups tested.     

In vitro activities of 10 antifungal drugs against 508 dermatophyte strains

We have tested 508 strains belonging to 24 species of dermatophytes against 10 antifungal drugs following mainly the NCCLS (M38-P) standard for filamentous fungi. However, several important factors, such as the temperature (28 versus 35 degrees C) and time of incubation (4 to 10 days versus 21 to 74 h), have been modified. The antifungals used were itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, terbinafine, amphotericin B, fluconazole, UR-9825, and G-1. In general, with the exception of fluconazole and G-1, all antifungals were shown to be highly effective.     

In vitro metronidazole and tinidazole activities against metronidazole-resistant strains of Trichomonas vaginalis

The in vitro activities of tinidazole and metronidazole against Trichomonas vaginalis isolates clinically resistant to metronidazole were compared. Minimal lethal concentrations (MLCs) of tinidazole were significantly lower than MLCs of metronidazole. Increased metronidazole resistance correlated with increased tinidazole resistance. These data support a role for tinidazole in the treatment of trichomoniasis.     

In vitro activity of meropenem and four other antibiotics against 554 clinical strains obtained from Beijing in 1999

In 1999, a surveillance study was initiated in a hospital in Beijing to monitor the potency and spectrum of five extended-spectrum β-lactam antimicrobial agents (meropenem, imipenem, cefepime, ceftazidime, and cefoperazone/sulbactam) tested against 554 strains of bacteria. Five groups of organisms were tested by the E-test method, with results validated by concurrent quality control strain analysis. Results were tabulated, and 100% of quality assurance tests (16/16 tests) were within ranges recommended by the National Committee for Clinical Laboratory Standards. Of the five β-lactam drugs tested, meropenem and imipenem were the most active against all isolates tested. Overall, the rank order of activity of the five agents was: meropenem (94.6% susceptible) > imipenem (90.1%) > cefepime (77.6%), cefoperazone/sulbactam (77.5%), ceftazidime (76.6%). Ninety-five percent of Enterobacter were to meropenem, while 82% were susceptible to imipenem. Meropenem was more active than imipenem against Pseudomonas aeruginosa. The minimum inhibitory concentration (MIC) of meropenem was eightfold lower than that of imipenem. Meropenem had excellent activity against Haemophilus influenzae, Streptococcus pneumoniae, and oxacillin-susceptible staphylococci. Received: March 16, 2000 / Accepted: July 5, 2000     

In vitro activities of antibiotics against Plasmodium falciparum are inhibited by iron

The in vitro activities of cyclines (tetracycline, doxycycline, minocycline, oxytetracycline, and rolitetracycline), macrolides (erythromycin, spiramycin, roxithromycin, and lincomycin), quinolones (norfloxacin and ofloxacin), rifampin, thiamphenicol, tobramycin, metronidazole, vancomycin, phosphomycin, and cephalosporins (cephalexin, cefaclor, cefamandole, cefuroxime, ceftriazone, cefotaxime, and cefoxitin) were evaluated on Plasmodium falciparum clones, using an isotopic, micro-drug susceptibility test. Only tetracyclines, macrolides, quinolones, and rifampin demonstrated in vitro activity against P. falciparum, which increased after a prolonged exposure (96 or 144 h). In the presence of iron (FeCl(3)), only the activities of tetracyclines and norfloxacin were decreased. Their in vitro activity against intraerythrocytic stages of multidrug-resistant P. falciparum and their efficacy in vivo favor the use of antibiotics as antimalarial drugs. However, due to their slow antimalarial action and to the fact that they act better after prolonged contact, they probably need to be administered in conjunction with a rapidly acting antimalarial drug, such as a short course of chloroquine or quinine.     

In vitro activities of three nonfluorinated quinolones against representative bacterial isolates

In vitro susceptibility tests were performed to document the inhibitory activities of three nonfluorinated quinolone (NFQ) compounds (PGE 9262932, PGE 9509924, and PGE 4175997) compared to those of ciprofloxacin, levofloxacin, and trovafloxacin against 3,030 bacterial isolates. The spectra of the NFQ agents included most gram-positive species as well as quinolone-susceptible Enterobacteriaceae. Ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus strains were inhibited by the NFQ series at < or =1.0 microg/ml. The NFQ compounds were not very active against Pseudomonas aeruginosa and most other nonfermentative gram-negative bacilli. Against other species, the potency of the NFQ agents was similar to that of trovafloxacin. Continued investigation of the NFQ compounds seems to be warranted.     

In vitro activities of doxycycline and enrofloxacin against European Chlamydia psittaci strains from turkeys.

The in vitro susceptibility of 14 European Chlamydia psittaci strains from turkeys to the antibiotics doxycycline and enrofloxacin was tested. For doxycycline the MIC ranged from 0.05 to 0.2 microg/ml, with an average of 0.1 microg/ml. For enrofloxacin the MIC was 0.25 microg/ml. Acquired resistance was not detected against doxycycline and enrofloxacin.