In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C. pneumoniae

The in vitro activities of iclaprim, a novel dihydrofolate reductase inhibitor, azithromycin, and levofloxacin were tested against 10 strains of Chlamydia trachomatis and 10 isolates of Chlamydia pneumoniae. For C. trachomatis and C. pneumoniae, the iclaprim MIC and minimal bactericidal concentration at which 90% of isolates were inhibited (MIC(90) and MBC(90)) were 0.5 micro g/ml, compared to an azithromycin MIC(90) and MBC(90) of 0.125 micro g/ml and levofloxacin MIC(90)s and MBC(90)s of 1 micro g/ml for C. trachomatis and 0.5 micro g/ml for C. pneumoniae.     

战创伤涂膜剂对厌氧菌体外抗菌实验研究

目的测定战创伤涂膜剂对产气荚膜梭菌（有芽孢菌）和脆弱拟杆菌（无芽孢菌）标准菌株的最低抑菌浓度（minimum inhibitory concentration,MIC）和最低杀菌浓度（minimum bactericidal concentration,MBC）。方法应用培养基将涂膜剂、氯已定甲硝唑乳膏稀释至不同浓度,分别加入产气荚膜梭菌和脆弱拟杆菌悬液,控制菌液浓度为10^5 efu／ml,厌氧培养后观察细菌生长情况,确定两药的MIC和MBC并进行比较。结果涂膜剂体外对脆弱拟杆菌、产气荚膜梭菌MIC均为1μg／ml,MBC分别为1μg／ml、2μg/ml。氯已定甲硝唑乳膏对脆弱拟杆菌、产气荚膜梭菌MIC分别为4μg／ml、1μg／ml,MBC为8μg／ml、2μg／ml。两药杀菌率均〉99％。结论涂膜剂对有芽孢和无芽孢类厌氧菌有良好的抑落、杀菌作用。     

战创伤涂膜剂对常见化脓菌的抗菌活性研究

目的测定战创伤涂膜剂对常见化脓菌的最低抑菌浓度（minimum inhibitory concentration,MIC）和最低杀菌浓度（minimum bactericidal concentration,MBC）。方法以培养基稀释战创伤涂膜剂、氯己定甲硝唑乳膏至不同浓度,分别加入化脓菌标准菌株大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、奇异变形杆菌悬液,菌液浓度为10^5cfu／ml,培养后观察细菌生长情况,确定两药的MIC和MBC并进行比较。结果战创伤涂膜剂对大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、奇异变形杆菌的MIC分别为0．0625μg／ml、2μg／ml、4μg／ml、8μg／ml,MBC分别为0．125μg／ml、4μg／ml、4μg／ml、8μg／ml。氯己定甲硝唑乳膏对大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、奇异变形杆菌的MIC分别为1μg／ml、8μg／ml、〉32μg／ml、〉32μg／ml,MBC分别为2μg／ml、16μg／ml、〉32μg／ml、〉32μg／ml。两药对金黄色葡萄球菌的杀菌率均达到99％以上。结论战创伤涂膜剂对常见化脓菌有良好的抑菌、杀菌作用。     

两种植物挥发油体外抗菌作用试验观察

目的观察金银花和山楂果核挥发油体外抗菌效果,为实际应用提供科学依据。方法采用稀释法对两种植物挥发油体外最小抑菌浓度和最小杀菌浓度进行了测定。结果金银花挥发油对革兰阴性菌株的MIC50和MIC90值均≥128μg/ml,对金黄色葡萄球菌MIC90值≥128μg/ml、MIC50值为64μg/ml。山楂果核挥发油对所有试验菌株的MIC50值在16～64μg/ml范围;MIC90值在64～128μg/ml。山楂果核挥发油作用15 min,对大肠杆菌和金黄色葡萄球菌MBC值在32～64μg/ml范围;金银花挥发油作用60 min,对上述两种细菌MBC值为64μg/ml。结论两种植物挥发油对试验菌株都具有良好的体外抗菌效果,但其MIC和MBC值均明显高于两种对照药物。     

Bactericidal versus Bacteriostatic Antibiotic Therapy of Experimental Pneumococcal Meningitis in Rabbits

A rabbit model of pneumococcal meningitis was used to examine the importance of bactericidal vs. bacteriostatic antimicrobial agents in the therapy of meningitis 112 animals were infected with one of two strains of type III Streptococcus pneumoniae. Both strains were exquisitely sensitive to ampicillin, minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC)<0.125 μg/ml. The activity of chloramphenicol against the two strains varied: strain₁—MIC 2 μg/ml, MBC 16 μg/ml; strain₂—MIC 1 μg/ml, MBC 2 μg/ml. Animals were treated with either ampicillin or chloramphenicol in dosages that achieved a peak bactericidal effect in cerebrospinal fluid (CSF) for ampicillin against both strains. Two different dosages were used for chloramphenicol. The first dosage achieved a peak CSF concentration of 4.4±1.1 μg/ml that produced a bacteriostatic effect against strain₁ and bactericidal effect against strain₂. The second dosage achieved a bactericidal effect against both strains (mean peak CSF concentration 30.0 μg/ml). All animals were treated intramuscularly three times a day for 5 d. CSF was sampled daily and 3 d after discontinuation of therapy for quantitative bacterial cultures. Results demonstrate that only antimicrobial therapy that achieved a bactericidal effect in CSF was associated with cure. Over 90% of animals treated with one of the bactericidal regimens (i.e., animals in which the bacterial counts in CSF dropped >5 log₁₀ colony-forming units [cfu]/ ml after 48 h) had sterile CSF after 5 d of treatment. On the other hand, the regimen that achieved bacteriostatic concentrations (CSF drug concentrations between the MIC and MBC) produced a drop of 2.4 log₁₀ cfu/ml by 48 h; however, none of the animals that survived had sterile CSF after 5 d. These studies clearly demonstrate in a strictly controlled manner that maximally effective antimicrobial therapy of experimental pneumococcal meningitis depends on achieving a bactericidal effect in CSF.     

替硝唑对厌氧菌体外抗菌活性的观察研究

目的 测定替硝唑对产气荚膜梭菌（有芽孢菌）和脆弱拟杆菌（无芽孢菌）标准菌株的最低抑菌浓度（mininmm inhibitory concentration,M1C）和最低杀菌浓度（minimum bactericidal concentration,MBC）。方法应用培养基稀释替硝唑至不同浓度,然后分别加入产气荚膜梭菌及脆弱拟杆菌悬液,菌液浓度为10^5cfu／ml,厌氧培养后观察细菌生长情况,确定MIC和MBC。结果替硝唑对脆弱拟杆菌、产气荚膜梭菌的MIC均为1μg／ml,MBC均为2μg／ml。结论替硝唑对有芽孢和无芽孢类厌氧菌都有良好的抑菌、杀菌作用。     

Antimicrobial activity of daptomycin tested against Staphylococcus aureus with vancomycin MIC of 2 μg/mL isolated in the United States and European hospitals (2006–2008)

We evaluated the activity of daptomycin (minimum inhibitory [MIC] and bactericidal [MBC] concentration) against Staphylococcus aureus strains with elevated (2 μg/mL) vancomycin MIC values. A total of 410 contemporary clinical S. aureus isolates (282 from the United States and 128 from Europe) with vancomycin MIC values of 2 μg/mL were tested by reference broth microdilution method. Vancomycin MBC and the presence of vancomycin-heteroresistant population (heterogeneous vancomycin-intermediate S. aureus [hVISA]) were evaluated in 31 randomly selected strains. Overall, 97.3% of isolates were susceptible to daptomycin (MIC₉₀, 0.5 μg/mL). Daptomycin exhibited potent bactericidal activity with MBC values at the MIC concentration (74.2%) or 1 log₂ dilution above the MIC (25.8%). In contrast, vancomycin MBC was ≥32 μg/mL in 12.9% of strains tolerance, and 25.8% of strains tested positive for hVISA (AB BIODISK GRD Etest, Solna, Sweden). In conclusion, S. aureus strains with vancomycin MIC of 2 μg/mL showed high rates of hVISA and vancomycin tolerance. Daptomycin retained potent bactericidal activity against S. aureus with decreased susceptibility to vancomycin.     

Role of rifampin against Propionibacterium acnes biofilm in vitro and in an experimental foreign-body infection model

Propionibacterium acnes is an important cause of orthopedic-implant-associated infections, for which the optimal treatment has not yet been determined. We investigated the activity of rifampin, alone and in combination, against planktonic and biofilm P. acnes in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration (MBC) were 0.007 and 4 μg/ml for rifampin, 1 and 4 μg/ml for daptomycin, 1 and 8 μg/ml for vancomycin, 1 and 2 μg/ml for levofloxacin, 0.03 and 16 μg/ml for penicillin G, 0.125 and 512 μg/ml for clindamycin, and 0.25 and 32 μg/ml for ceftriaxone. The P. acnes minimal biofilm eradication concentration (MBEC) was 16 μg/ml for rifampin; 32 μg/ml for penicillin G; 64 μg/ml for daptomycin and ceftriaxone; and ≥128 μg/ml for levofloxacin, vancomycin, and clindamycin. In the animal model, implants were infected by injection of 10⁹ CFU P. acnes in cages. Antimicrobial activity on P. acnes was investigated in the cage fluid (planktonic form) and on explanted cages (biofilm form). The cure rates were 4% for daptomycin, 17% for vancomycin, 0% for levofloxacin, and 36% for rifampin. Rifampin cured 63% of the infected cages in combination with daptomycin, 46% with vancomycin, and 25% with levofloxacin. While all tested antimicrobials showed good activity against planktonic P. acnes, for eradication of biofilms, rifampin was needed. In combination with rifampin, daptomycin showed higher cure rates than with vancomycin in this foreign-body infection model.     

醋酸氯己定体外抗菌作用的实验观察

目的观察醋酸氯己定体外抗菌作用。方法采用肉汤稀释法,测定了醋酸氯己定对4种条件致病菌和一种厌氧菌的抗菌效果。结果醋酸氯己定对脆弱拟杆菌MIC为4μg/ml,MBC为8μg/ml;对产气荚膜梭菌的MIC为1μg/ml,MBC为2μg/ml。醋酸氯己定对金黄色葡萄球菌MIC为0.0625μg/ml,MBC为0.125μg/ml;对大肠埃希菌MIC为2μg/ml,MBC为4μg/ml;对铜绿假单胞菌MIC为4μg/ml,MBC为4μg/ml;奇异变形杆菌MIC为8μg/ml,MBC为8μg/ml。结论醋酸氯己定对常见条件致病菌和厌氧菌都有良好的体外抗菌作用。     

纳米银妇科抑菌喷剂体外抗菌效果的观察

目的观察纳米银妇科抑菌喷剂的体外抗菌效果,为实际应用提供依据。方法采用抑菌环试验和悬液定量试验方法,对该纳米银妇科抑菌喷剂体外抗菌效果进行实验室观察。结果纳米银妇科抑菌喷剂对大肠杆菌、金黄色葡萄球菌、铜绿假单胞菌和白色念珠菌的最低抑菌浓度分别为3.15μg/ml、6.3μg/ml、3.15μg/ml和6.3μg/ml,最低杀菌浓度分别为12.6μg/ml、25.2μg/ml、12.6μg/ml和25.2μg/ml。银含量为25.2μg/ml的纳米银妇科抑菌喷剂对上述四个菌种作用2 min,杀菌率均达到90%以上。结论纳米银妇科抑菌喷剂对大肠杆菌、金黄葡萄球菌、铜绿假单胞菌和白色念珠菌均具有较强的抑杀作用。     

In Vitro Activities of Cefminox against Anaerobic Bacteria Compared with Those of Nine Other Compounds

The agar dilution MIC method was used to test the activity of cefminox, a β-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active β-lactam, with an MIC at which 50% of isolates are inhibited (MIC₅₀) of 1.0 μg/ml and an MIC₉₀ of 16.0 μg/ml. Other β-lactams were less active, with respective MIC₅₀s and MIC₉₀s of 2.0 and 64.0 μg/ml for cefoxitin, 2.0 and 128.0 μg/ml for cefotetan, 2.0 and 64.0 μg/ml for moxalactam, 4.0 and >128.0 μg/ml for ceftizoxime, 16.0 and >128.0 μg/ml for cefotiam, 8.0 and >128.0 μg/ml for cefamandole, and 4.0 and 128.0 μg/ml for cefoperazone. The clindamycin MIC₅₀ and MIC₉₀ were 0.5 and 8.0 μg/ml, respectively, and the metronidazole MIC₅₀ and MIC₉₀ were 1.0 and 4.0 μg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC₉₀, 2.0 μg/ml), Bacteroides thetaiotaomicron (MIC₉₀, 4.0 μg/ml), fusobacteria (MIC₉₀, 1.0 μg/ml), peptostreptococci (MIC₉₀, 2.0 μg/ml), and clostridia, including Clostridium difficile (MIC₉₀, 2.0 μg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4× the MIC and cefoperazone at 8× the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2× the MIC produced the most rapid effect, with 90% killing of all strains.     

Influence of inoculum size on activity of cefoperazone, cefotaxime, moxalactam, piperacillin, and N-formimidoyl thienamycin (MK0787) against Pseudomonas aeruginosa.

Forty clinical isolates of Pseudomonas aeruginosa were tested for their susceptibility to cefoperazone, cefotaxime, moxalactam, piperacillin, N-formimidoyl thienamycin (MK0787), and gentamicin at three different inocula. At an inoculum of 5 x 10(3) colony-forming units (CFU) per ml, the minimum inhibitory concentrations (in micrograms per milliliter) for 90% of isolates (MIC90) were as follows: gentamicin, 1; N-formimidoyl thienamycin, 2; cefoperazone, 4; piperacillin, 8; moxalactam, 16; and cefotaxime, 16. When the inoculum was increased to 5 x 10(5) CFU/ml, the MIC90 for all drugs tested increased. Among the beta-lactam antibiotics, N-formimidoyl thienamycin and cefoperazone had the lowest MIC90 (8 micrograms/ml) at this inoculum. When the inoculum was increased further to 5 x 10(7) CFU/ml, an MIC90 could be determined only for gentamicin and N-formimidoyl thienamycin (4 and 8 micrograms/ml, respectively). Indeed, the MIC50 for moxalactam, cefotaxime, cefoperazone, and piperacillin was 128 micrograms/ml or more at this inoculum. The minimum bactericidal concentration for 90% of isolates (MBC90) at an inoculum of 5 x 10(5) CFU/ml ranged from 8 micrograms/ml for gentamicin and N-formimidoyl thienamycin to 128 micrograms/ml for cefotaxime. At the highest inoculum, however, whereas the MBC90 for gentamicin and N-formimidoyl thienamycin remained at 8 micrograms/ml, the MBC90 for each of the other drugs was greater than 128 micrograms/ml. N-Formimidoyl thienamycin was the only drug tested for which an MIC100 and MBC100 (MIC and MBC for 100% of isolates) could be determined, and these were not significantly different from the MIC90 and MCB90.     

Antibacterial activity of sphingoid bases and fatty acids against Gram-positive and Gram-negative bacteria

There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity--the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid--against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. D-sphingosine (MBC range, 0.3 to 19.6 μg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 μg/ml), and phytosphingosine (MBC range, 3.3 to 62.5 μg/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.     

Oritavancin activity against vancomycin-susceptible and vancomycin-resistant Enterococci with molecularly characterized glycopeptide resistance genes recovered from bacteremic patients, 2009-2010

Oritavancin exhibited potent activity against vancomycin-susceptible (MIC(50) and MIC(90), 0.015/0.03 μg/ml) and vanB-carrying E. faecalis isolates (MIC(50) and MIC(90), 0.015 and 0.015 μg/ml). Higher (16- to 32-fold) MIC(50)s and MIC(90)s for vanA-harboring E. faecalis were noted (MIC(50) and MIC(90), 0.25 and 0.5 μg/ml), although oritavancin inhibited all strains at ≤ 0.5 μg/ml. Vancomycin-susceptible and vanB-carrying E. faecium strains (MIC(50) and MIC(90), ≤ 0.008 and ≤ 0.008 μg/ml for both) were very susceptible to oritavancin, as were VanA-producing isolates (MIC(50) and MIC(90), 0.03 and 0.06 μg/ml). Oritavancin exhibited good in vitro potency against this collection of organisms, including vancomycin-resistant enterococci.     

Efficacy of human-simulated exposures of tomopenem (formerly CS-023) in a murine model of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infection

Tomopenem (formerly CS-023) is a novel carbapenem with improved activity against diverse hospital pathogens, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), and has a half-life about twice longer than the half-lives of other carbapenems such as imipenem and meropenem. Our objective in this study was to estimate the efficacy of tomopenem in humans by human-simulated exposures in a neutropenic murine thigh infection model against 9 clinical isolates of P. aeruginosa with MICs of 4 to 32 μg/ml and 9 clinical isolates of MRSA with MICs of 4 to 16 μg/ml. Human-simulated dosing regimens in neutropenic mice were designed to approximate the cumulative percentage of a 24-h period that the free drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f%T(MIC)) observed with tomopenem at 750 and 1,500 mg given as a 0.5-h infusion three times a day (TID) in humans. As reported previously, there was no difference between the target values of P. aeruginosa and MRSA required for efficacy (K. Sugihara et al., Antimicrob. Agents Chemother. 54:5298-5302, 2010). Tomopenem at 750 mg showed bactericidal or bacteriostatic effects against 10 of 11 strains of P. aeruginosa and MRSA with MICs of ≤ 8 μg/ml (f%T(MIC) ≥ 41), and tomopenem at 1,500 mg showed bactericidal effects against 16 of 17 strains of P. aeruginosa and MRSA with MICs of ≤ 16 μg/ml (f%T(MIC) ≥ 43). Meropenem at 1,000 mg TID was tested for comparison purposes and showed bactericidal or bacteriostatic effects against 3 of 4 strains of P. aeruginosa with MICs of ≤ 4 μg/ml (f%T(MIC) ≥ 33). From these results, tomopenem is expected to be effective with an f%T(MIC) of over 40 against P. aeruginosa and MRSA strains with MICs of ≤ 8 μg/ml at doses of 750 mg TID and strains with MICs of ≤ 16 μg/ml at doses of 1,500 mg TID.     

Antimicrobial susceptibility of Capnocytophaga.

Capnocytophaga (Bacteroides ochraceus, Center for Disease Control biogroup DF-1) is associated with sepsis in granulocytopenic patients and is isolated in large numbers from the affected periodontal pockets in patients with juvenile periodontosis. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of 17 antimicrobial agents for 13 strains of Capnocytophaga organisms were determined. In addition, the ratio of the MBC to the MIC for each antimicrobial agent was determined for each strain. At concentrations of 1 microgram/ml or less, penicillin, ampicillin, carbenicillin, erythromycin, and clindamycin killed 90% of the strains. At concentrations of 3.12 microgram/ml or less, tetracycline, metronidazole, cefoxitin, and chloramphenicol killed 90% of the strains. None of the aminoglycosides tested demonstrated antibacterial activity at 50 microgram/ml. Penicillin, ampicillin, carbenicillin, and cefoxitin exhibited MBC/MIC ratios of 4 or less with all strains. Erythromycin, tetracycline, and metronidazole exhibited MBC/MIC ratios of 4 or less for 12 of 13 strains. The MICs of cephalothin and cefazolin for 90% of the strains were 25 and 50 microgram/ml, respectively. The MBC/MIC ratios for these drugs were 4 or less for 12 of 13 and 7 of 13 strains, respectively. The MIC of cefamandole for 90% of the strains was 3.12 microgram/ml; however, only nine strains had an MBC/MIC ratio of 4 or less.     

Pharmacokinetics and pharmacodynamics of two multiple-dose piperacillin-tazobactam regimens.

The pharmacokinetics and pharmacodynamics of two multiple-dose regimens of piperacillin-tazobactam (3.375 g every 6 h and 4.5 g every 8 h) were evaluated at steady state for 12 healthy adult volunteers. Inhibitory and bactericidal activities for the two regimens were determined with five American Type Culture Collection (ATCC) organisms (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis). The percentage of time that plasma concentrations remained above the MIC (T > MIC) for each organism and dosage regimen was calculated. Areas under the inhibitory (AUIC0-24) and bactericidal activity (AUBC0-24) curves were calculated with the trapezoidal rule by using the reciprocal of the inhibitory and bactericidal titers determined for each dosage regimen. In order to assess the validity of predicted measures of bactericidal (AUC0-24/MBC) and inhibitory (AUC0-24/MIC) activity to determine bacteriological response to beta-lactam antimicrobial agents, AUC0-24/MBC and AUC0-24/MIC values were compared with measured AUBC0-24 and AUIC0-24 values. Total body clearance values were equivalent for piperacillin (183.96 +/- 22.66 versus 181.72 +/- 19.54 ml/min/1.73 m2, P > 0.05) and tazobactam (184.71 +/- 19.89 versus 184.87 +/- 18.35 ml/min/1.73 m2, P > 0.05) following the administration of the 3.375-g-every-6-h and 4.5-g-every-8-h dosages, respectively. Comparison of area under the plasma concentration-time curve (AUC0-24) for piperacillin (967.74 +/- 135.56 microg x h/ml versus 978.88 +/- 140.96 microg x h/ml) and tazobactam (120.14 +/- 15.78 microg x h/ml versus 120.01 +/- 16.22 microg x h/ml) revealed no significant differences (P > 0.05) between the 3.375-g-every-6-h and 4.5-g-every-8-h regimens, respectively. Both regimens provided T > MIC values of > 60% for all organisms tested. Measured values of bactericidal (AUBC) and inhibitory (AUIC) activity were significantly different (P < 0.05) from predicted values (AUC0-24/MBC and AUC0-24/MIC) for all organisms studied with the exception of the bactericidal activity for P. aeruginosa and S. aureus. Additionally, ATCC organisms possessing the same MICs and MBCs exhibited great differences in measured AUBC0-24 and AUIC0-24 values. Reasons for this difference may be inherent differences in organism specific susceptibility.     

Activities and Time-Kill Studies of Selected Penicillins, β-Lactamase Inhibitor Combinations, and Glycopeptides against Enterococcus faecalis

The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, vancomycin, and teicoplanin were tested against 212 Enterococcus faecalis strains (9 β-lactamase producers) by standard agar dilution MIC testing (10⁴ CFU/spot). The MICs at which 50 and 90% of the isolates were inhibited (MIC₅₀s and MIC₉₀s, respectively) were as follows (μg/ml): piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8; ticarcillin, 64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and 2; ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin, 0.5 and 1. Agar dilution MIC testing of the nine β-lactamase-positive strains with an inoculum of 10⁶ CFU/spot revealed higher β-lactam MICs (piperacillin, 64 to >256 μg/ml; ticarcillin, 128 to >256 μg/ml; and ampicillin, 16 to 128 μg/ml); however, MICs with the addition of inhibitors were similar to those obtained with the lower inoculum. Time-kill studies of 15 strains showed that piperacillin-tazobactam was bactericidal (99.9% killing) for 14 strains after 24 h at four times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Ampicillin gave 99.9% killing of 14 β-lactamase-negative strains after 24 h at eight times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Killing by ticarcillin-clavulanate was slower than that observed for piperacillin-tazobactam, relative to the MIC. For the one β-lactamase-producing strain tested by time-kill analysis with a higher inoculum, addition of the three inhibitors (including sulbactam) to each of the β-lactams resulted in bactericidal activity at 24 h at two times the MIC. For an enzyme-negative strain, addition of inhibitors did not influence kinetics. Kinetics of vancomycin and teicoplanin were significantly slower than those of the β-lactams, with bactericidal activity against 6 strains after 24 h at eight times the MIC, with 90% killing of 12 and 14 strains, respectively, at four times the MIC. Slower-kill kinetics by both glycopeptides were observed at earlier periods.     

Antistaphylococcal activity of dalbavancin, an experimental glycopeptide

Dalbavancin, tested against 146 staphylococci, was more potent than other drugs tested, with an MIC at which 50% of staphylococci were inhibited of 0.03 μg/ml and an MIC at which 90% of staphylococci were inhibited of 0.06 μg/ml by microdilution. For all strains, MICs of vancomycin, linezolid, ranbezolid, oritavancin, daptomycin, and quinupristin-dalfopristin were ≤4.0 μg/ml. Dalbavancin was bactericidal at four times the MIC against all six strains tested.     

In vitro and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone

The in vitro and in vivo activity of T-3912, a novel non-fluorinated topical quinolone, was compared with that of nadifloxacin, ofloxacin, levofloxacin, clindamycin, erythromycin and gentamicin. The in vitro activity of T-3912 against methicillin-susceptible Staphylococcus aureus, ofloxacin-resistant and methicillin-resistant S. aureus, Staphylococcus epidermidis, ofloxacin-resistant S. epidermidis, penicillin-resistant Streptococcus pneumoniae and Propionibacterium acnes was four-fold to 16 000-fold greater than that of other agents at the MIC90 for the clinical isolates. The activity of T-3912 was not influenced by grlA mutation in S. aureus, and the degree of MIC increase of T-3912 for grlA-gyrA double and triple mutants was lowest among the quinolones tested (nadifloxacin, levofloxacin and ofloxacin). The inhibitory activity of T-3912 was compared with other quinolones for DNA gyrase and topoisomerase IV of S. aureus SA113. T-3912 showed the greatest inhibitory activity for both enzymes among the quinolones tested. The isolation frequency of spontaneous mutants resistant to T-3912 was < 1.7 x 10(-9) and < 2.0 x 10(-9) for S. aureus SA113 and P. acnes JCM 6425, respectively. Furthermore, resistance to T-3912 could not be clearly detected in the 28th transfer by the serial passage method. T-3912 exhibited more potent bactericidal activity against S. aureus and P. acnes than nadifloxacin and clindamycin in a short time period. T-3912 in a 1% gel formulation showed good therapeutic activity against a burn infection model caused by S. aureus SA113, P. acnes JCM6425 and multidrug-resistant S. aureus F-2161. These results indicate that T-3912 is potentially a useful quinolone for the treatment of skin and soft-tissue infections and that its potent bactericidal activity might be able to shorten the treatment period.