In vitro activities of rifamycin derivatives ABI-1648 (Rifalazil,KRM-1648), ABI-1657, and ABI-1131 against Chlamydia trachomatis and recent clinical isolates of Chlamydia pneumoniae

ABI-1648 (rifalazil) is a semisynthetic rifamycin with potent bactericidal activity against intracellular respiratory bacteria, including Mycobacterium tuberculosis, and a long half-life (approximately 60 h) and thus can be administered once weekly. We therefore tested the in vitro activities of ABI-1648, its derivatives ABI-1657 and ABI-1131, azithromycin, and levofloxacin against 10 strains of Chlamydia trachomatis and 10 recent clinical isolates of Chlamydia pneumoniae. The MICs at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed for ABI-1648, ABI-1657, and ABI-1131 were 0.0025 micro g/ml for C. trachomatis and 0.00125 to 0.0025 micro g/ml for C. pneumoniae. ABI-1648, ABI-1657, and ABI-1131 were 10- to 1,000-fold more active than azithromycin and levofloxacin.     

In vitro evaluation of activities of azithromycin, erythromycin, and tetracycline against Chlamydia trachomatis and Chlamydia pneumoniae.

The in vitro activities of azithromycin (CP-62,993; Pfizer), erythromycin, and tetracycline were evaluated by inhibiting Chlamydia trachomatis and Chlamydia pneumoniae, formerly TWAR, propagation in vitro in McCoy cells, HeLa cells, and HL cells. Eleven clinical isolates of C. trachomatis (serovars D, E, F, J, K, and L2) and four strains of C. pneumoniae were tested with an inoculum of 10(3) inclusion-forming units in a 96-well microtiter plate. The MIC ranges of these antimicrobial agents against C. trachomatis were as follows: azithromycin, 0.125 to 0.5 microgram/ml; erythromycin, 0.25 to 0.1 microgram/ml; and tetracycline, 0.0625 to 1.0 microgram/ml. The MBC ranges, calculated from passage into antibiotic-free medium, were as follows: azithromycin, 0.125 to 4.0 micrograms/ml; erythromycin, 0.5 to 8.0 micrograms/ml; and tetracycline, 0.0625 to 4.0 micrograms/ml. The MIC ranges for C. pneumoniae in both HeLa and HL cells were as follows: azithromycin, 0.125 to 1.0 micrograms/ml; erythromycin, 0.0625 to 1.0 microgram/ml; and tetracycline, 0.125 to 1.0 microgram/ml. The MBC ranges were as follows: azithromycin, 0.25 to 1.0 microgram/ml; erythromycin, 0.25 to 1.0 microgram/ml; and tetracycline, 0.125 to 4.0 micrograms/ml. From the results of this in vitro study, azithromycin appears to be an effective antibiotic comparable to tetracycline and erythromycin for use in the treatment of both C. trachomatis and C. pneumoniae infections.     

In vitro activity of a new antibiotic,NVP-PDF386 (VRC4887), against Chlamydia pneumoniae

The in vitro activity of NVP-PDF386 (VRC4887), a novel new peptide deformylase inhibitor, and those of levofloxacin and clarithromycin were tested against 21 isolates of Chlamydia pneumoniae. The MIC at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by NVP-PDF386 for all isolates of C. pneumoniae were 0.008 micro g/ml (range, 0.008 to 0.015 micro g/ml) compared to 0.25 and 0.06 micro g/ml for levofloxacin and clarithromycin, respectively.     

In Vitro Activities of BMS-284756 against Chlamydia trachomatis and Recent Clinical Isolates of Chlamydia pneumoniae

The in vitro activities of BMS-284756 (a novel des-fluoroquinolone), levofloxacin, moxifloxacin, and clarithromycin were tested against 5 strains of Chlamydia trachomatis and 20 isolates of Chlamydia pneumoniae. The MIC at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by BMS-284756 for all isolates of C. pneumoniae and C. trachomatis was 0.015 microg/ml (range, 0.015 to 0.03 microg/ml). BMS-284756 was the most active quinolone tested.     

四种国产大环内酯类抗菌药物体外抗沙眼衣原体和肺炎衣原体敏感性研究

目的 研究国产必特螺旋霉素、乙酰螺旋霉素、红霉素和阿奇霉素等4种大环内酯类药物对于沙眼衣原体和肺炎衣原体体外药物敏感性试验,评估其抗衣原体作用,以指导临床用药.方法 细胞培养和免疫荧光包涵体染色技术测定4种国产大环内酯类抗菌药物对于沙眼衣原体和肺炎衣原体体外MIC.结果 对于沙眼血清型B,必特螺旋霉素、红霉素和阿奇霉素体外MIC为0.5μg/ml,乙酰螺旋霉素为4μg/ml.对于沙眼血清型D,必特螺旋霉素与阿奇霉素体外MIC均为0.25μg/ml,红霉素0.5μg/ml,乙酰螺旋霉素2μg/ml.对于肺炎衣原体,红霉素体外MIC≤0.016μg/ml,阿奇霉素和必特螺旋霉素均为0.032μg/ml,乙酰螺旋霉素0.5μg/ml.结论 国产必特螺旋霉素、红霉素和阿奇霉素体外抗沙眼衣原体(血清型B和D)和肺炎衣原体作用可靠,但乙酰螺旋霉素则较差.     

A comparative In vitro surveillance study of gemifloxacin activities against 2,632 recent Streptococcus pneumoniae isolates from across Europe, North America, and South America. The Gemifloxacin Surveillance Study Research Group

From 1997 to 1999, 94 study centers in 15 European, 3 North American, and 2 South American countries contributed 2,632 isolates of Streptococcus pneumoniae to an international antimicrobial susceptibility testing study. Only 62.0% of isolates were susceptible to penicillin, while 22.3% were penicillin intermediate and 15.6% were penicillin resistant. Resistance to trimethoprim-sulfamethoxazole (24.4%), azithromycin (26.0%), and clarithromycin (27.1%) was also highly prevalent. For the penicillin-resistant isolates (n = 411), the MICs at which 90% of isolates are inhibited (MIC(90)s) for gemifloxacin, levofloxacin, ofloxacin, clarithromycin, and azithromycin were 0.03, 1, 2, >16, and >64 microgram/ml, respectively. Similarly, for isolates resistant to both azithromycin and clarithromycin (n = 649), gemifloxacin, levofloxacin, ofloxacin, and penicillin MIC(90)s were 0.03, 1, 2, and 4 microgram/ml, respectively. Overall rates of resistance to trovafloxacin (0.3%), levofloxacin (0.3%), grepafloxacin (0.6%), and ofloxacin (0.7%) were low. For ofloxacin-intermediate and -resistant isolates (n = 142), gemifloxacin had the lowest MIC(90) (0.12 microgram/ml) compared to the MIC(90)s of trovafloxacin (0.5 microgram/ml), grepafloxacin (1 microgram/ml), and levofloxacin (2 microgram/ml). For all S. pneumoniae isolates tested, gemifloxacin MICs were 相似文献   

In vitro activity of azithromycin (CP-62,993) against Chlamydia trachomatis and Chlamydia pneumoniae.

The in vitro susceptibilities of 49 strains of Chlamydia trachomatis and 3 strains of Chlamydia pneumoniae to azithromycin and tetracycline or doxycycline were determined. The MIC of azithromycin ranged from < or = 0.06 to 1.0 micrograms/ml, the MIC of tetracycline ranged from 0.03 to 0.12 micrograms/ml, and the MIC of doxycycline ranged from 0.015 to 0.06 micrograms/ml against C. trachomatis. The MIC ranges for C. pneumoniae were 0.12 to 0.25 micrograms/ml for azithromycin and 0.06 to 0.12 micrograms/ml for tetracycline. All minimal chlamydicidal concentrations were either equal to the MIC or one or two dilutions higher. No strains resistant to these antibiotics were detected. In vitro activity shows that azithromycin is highly active against C. trachomatis and C. pneumoniae.     

In vitro activity of ABT 773, a new ketolide antibiotic, against Chlamydia pneumoniae

The in vitro activities of ABT 773, telithromycin (HMR 3647), azithromycin, clarithromycin, erythromycin, and levofloxacin were tested against 20 strains of Chlamydia pneumoniae. The MIC at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by ABT 773 were 0.015 microg/ml (range, 0.008 to 0.015 microg/ml). ABT 773 was the most active antibiotic tested in this study.     

Comparative in vitro activity of garenoxacin against Chlamydia spp

The in vitro susceptibilities of 33 isolates of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci to a new quinolone drug, garenoxacin (BMS-284756), in comparison with levofloxacin, ciprofloxacin, doxycycline, erythromycin and roxithromycin, were determined. Garenoxacin was the most active of the quinolone drugs tested, with identical MIC and MBC, which ranged from 0.007 to 0.03 mg/L. The MIC and MBC of the other two quinolones tested, levofloxacin and ciprofloxacin, were also identical, ranging from 0.25 to 2 mg/L. The MICs and MBCs of doxycycline, erythromycin and roxithromycin were also determined.     

In vitro activity of tosufloxacin (A-61827; T-3262) against selected genital pathogens.

The in vitro activity of tosufloxacin (A-61827; T-3262) against 15 clinical isolates of Chlamydia trachomatis and 31 recent clinical isolates of Neisseria gonorrhoeae, including 15 spectinomycin-resistant N. gonorrhoeae and 16 penicillinase-producing N. gonorrhoeae, was determined. Tosufloxacin was compared with doxycycline, ciprofloxacin, and temafloxacin against C. trachomatis. Susceptibility testing was performed by using McCoy cell monolayers. The in vitro activity of tosufloxacin against N. gonorrhoeae was compared with that of ciprofloxacin, temafloxacin, doxycycline, ceftriaxone, and spectinomycin by using an agar dilution method. Tosufloxacin was as active as temafloxacin against C. trachomatis (MIC for 90% of strains tested [MIC90], 0.25 microgram/ml; MBC for 90% of strains tested [MBC90], 0.25 microgram/ml) and was almost as active as doxycycline (MIC90, 0.06 microgram/ml; MBC90, 0.125 microgram/ml). Ciprofloxacin, temafloxacin, and tosufloxacin were extremely active against N. gonorrhoeae, including spectinomycin-resistant N. gonorrhoeae and penicillinase-producing N. gonorrhoeae, with MIC90s of 0.004, 0.015, and 0.008 microgram/ml, respectively. Ceftriaxone was slightly less active (MIC90, 0.03 microgram/ml), and doxycycline was the least active drug tested (MIC90, 4.0 micrograms/ml). Tosufloxacin and temafloxacin had excellent activity against the C. trachomatis and N. gonorrhoeae strains tested.     

In Vitro Activity of Nemonoxacin,a Novel Nonfluorinated Quinolone Antibiotic,against Chlamydia trachomatis and Chlamydia pneumoniae

The in vitro activities of nemonoxacin, levofloxacin, azithromycin, and doxycycline were tested against 10 isolates each of Chlamydia trachomatis and Chlamydia pneumoniae. The MICs at which 90% of the isolates of both C. trachomatis and C. pneumoniae were inhibited (MIC₉₀s) were 0.06 μg/ml (range, 0.03 to 0.13 μg/ml). The minimal bactericidal concentrations at which 90% of the isolates were killed by nemonoxacin (MBC₉₀s) were 0.06 μg/ml for C. trachomatis (range, 0.03 to 0.125 μg/ml) and 0.25 for C. pneumoniae (range, 0.015 to 0.5 μg/ml).     

In Vitro Activity of AZD0914, a Novel DNA Gyrase Inhibitor,against Chlamydia trachomatis and Chlamydia pneumoniae

The in vitro activities of AZD0914, levofloxacin, azithromycin, and doxycycline against 10 isolates each of Chlamydia trachomatis and Chlamydia pneumoniae were tested. For AZD0914, the MIC₉₀s for C. trachomatis and C. pneumoniae were 0.25 μg/ml (range, 0.06 to 0.5 μg/ml) and 1 μg/ml (range, 0.25 to 1 μg/ml), respectively, and the minimal bactericidal concentrations at which 90% of the isolates were killed (MBC₉₀s) were 0.5 μg/ml for C. trachomatis (range, 0.125 to 1 μg/ml) and 2 μg/ml for C. pneumoniae (range, 0.5 to 2 μg/ml).     

Comparative in-vitro activity of moxifloxacin, minocycline and azithromycin against Chlamydia spp.

The in-vitro activity of moxifloxacin, a new 8-methoxyquinolone, was compared with minocycline and azithromycin against 40 strains of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci. Both the MIC and the MBC of moxifloxacin ranged from 0.03 to 0.125 mg/L. MICs of minocycline ranged from 0.015 to 0.06 mg/L and MBCs between 0.03 and 0.25 mg/L. MICs of azithromycin ranged from 0.03 to 0.125 mg/L and the MBCs between 0.06 and 0.5 mg/L. MBC values of moxifloxacin were the same as MICs in 32 (80%) of 40 strains tested, whereas those of minocycline and azithromycin were two to four times higher than their MICs. These data confirm those previously obtained indicating that quinolones kill chlamydial strains at concentrations equivalent to their MICs.     

Macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes in the pediatric population in Germany during 2000-2001

In a nationwide study in Germany covering 13 clinical microbiology laboratories, a total of 307 Streptococcus pyogenes (mainly pharyngitis) and 333 Streptococcus pneumoniae (respiratory tract infections) strains were collected from outpatients less than 16 years of age. The MICs of penicillin G, amoxicillin, cefotaxime, erythromycin A, clindamycin, levofloxacin, and telithromycin were determined by the microdilution method. In S. pyogenes isolates, resistance rates were as follows: penicillin, 0%; erythromycin A, 13.7%; and levofloxacin, 0%. Telithromycin showed good activity against S. pyogenes isolates (MIC(90) = 0.25 micro g/ml; MIC range, 0.016 to 16 micro g/ml). Three strains were found to be telithromycin-resistant (MIC >/= 4 micro g/ml). Erythromycin-resistant strains were characterized for the underlying resistance genotype, with 40.5% having the efflux type mef(A), 38.1% having the erm(A), and 9.5% having the erm(B) genotypes. emm typing of macrolide-resistant S. pyogenes isolates showed emm types 4 (45.2%), 77 (26.2%), and 12 (11.9%) to be predominant. In S. pneumoniae, resistance rates were as follows: penicillin intermediate, 7.5%; penicillin resistant, 0%; erythromycin A, 17.4%; and levofloxacin, 0%. Telithromycin was highly active against pneumococcal isolates (MIC(90) 相似文献   

In vitro activities of ABT-773 and other antimicrobials against human mycoplasmas

The in vitro susceptibilities of 103 Mycoplasma pneumoniae isolates, 14 Mycoplasma hominis isolates, 12 Mycoplasma fermentans isolates, and 24 Ureaplasma species to ABT-773, an investigational ketolide, and seven other agents were determined. For M. pneumoniae, the ABT-773 MIC at which 90% of isolates are inhibited (MIC(90); or=16-fold lower than those of all three fluoroquinolones. Minimal bactericidal concentrations determined for a subgroup of organisms were 相似文献   

In vitro susceptibility of recent clinical isolates of Chlamydia trachomatis to macrolides and tetracyclines

We tested the in vitro activity of clarithromycin, azithromycin, roxithromycin, erythromycin, doxycycline, and tetracycline against 50 clinical isolates of Chlamydia trachomatis. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined in a tissue culture system using cycloheximide treated McCoy cells. MIC values for all the isolates were < or =0.015 microg/ml for clarithromycin, < or =0.125 microg/ml for roxithromycin and azithromycin, and < or =0.25 microg/ml for erythromycin and doxycycline. Almost half of the isolates (44%) were inhibited only by a concentration of 0.5 microg/ml of tetracycline. MBC as high as 4 microg/ml was displayed by doxycycline and tetracycline against 8% and 4% of the isolates respectively of the agents recommended by the Center for Disease Control as drugs of choice for the treatment of chlamydial infections, azithromycin exhibited a markedly better in-vitro activity than did erythromycin and doxycycline.     

The in-vitro activity of two new quinolones: rufloxacin and MF 961.

The in-vitro activity of two new quinolone antimicrobials, rufloxacin and MF 961, together with the desmethylated metabolite of rufloxacin (MF 922) were compared with other orally administered agents against 622 bacterial strains. Against Enterobacteriaceae and Pseudomonas aeruginosa rufloxacin was generally active (MIC90 1-8 mg/L) with the exception of Klebsiella and Serratia spp. (MIC90 32 mg/L and Enterobacter spp. (MIC90) 64 mg/L. The respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis were susceptible to rufloxacin (MIC90 0.5 and 1 mg/L respectively) but Streptococcus pneumoniae was less susceptible (MIC90 32 mg/L). Staphylococcus aureus were susceptible to rufloxacin (MIC90 2 mg/L). The rufloxacin metabolite MF 922 was generally as active as its parent. MF 961 was usually two-fold more active than rufloxacin. All three compounds were four to 16 times less active than norfloxacin, but rufloxacin was as active or somewhat more active than norfloxacin against Staphylococcus spp. Any strains showing decreased susceptibility to other quinolones exhibited cross resistance to these new agents. The MBC of rufloxacin and MF 922 was within one dilution of the MIC and human serum had little effect upon the activity of both agents. The protein binding of rufloxacin and MF 922 at 1 and 10 mg/L were 55% and 63.8% and 30.3% and 32.6% respectively. The activity of rufloxacin against four strains of Chlamydia trachomatis and one strain of Chlamydia pneumoniae was determined. The MICs for C. trachomatis were 4-8 mg/L and 4 mg/L for C. pneumoniae.     

Prospective,multicenter surveillance study of Candida glabrata: fluconazole and itraconazole susceptibility profiles in bloodstream,invasive, and colonizing strains and differences between isolates from three urban teaching hospitals in New York City (Candida Susceptibility Trends Study, 1998 to 1999)

Since the 1990s, the substantial increase in the rate of Candida glabrata infections has become a serious problem. As most C. glabrata infections arise from the host's endogenous microflora, the present prospective, multicenter analysis included all clinical isolates associated with colonization and with systemic and hematogenous candidiasis. Among 347 C. glabrata isolates, the overall rates of resistance to fluconazole (MIC > or = 64 micro g/ml) and itraconazole (MIC > or = 1 micro g/ml) were 10.7 and 15.2%, respectively, although for half (n = 148) of the itraconazole-susceptible isolates the MICs (0.25 to 0.5 micro g/ml) were in the susceptible-dependent upon dose range. Fluconazole resistance was more common among C. glabrata isolates obtained from centers caring for patients with cancer (MICs at which 90% of isolates are inhibited [MIC(90)s] = 32 micro g/ml) or AIDS (MIC(90)s > 64 micro g/ml) than among C. glabrata isolates from a community-based university medical center (MIC(90)s = 16 micro g/ml) (P = 0.001). Thirty-three bloodstream isolates and those obtained from other body sites had similar in vitro susceptibility profiles. The fluconazole MIC(90)s (< or =16 micro g/ml) for C. glabrata yeast isolates from the gastrointestinal tract were lower than those (> or =64 micro g/ml) for C. glabrata isolates from respiratory and urinary tract samples (P = 0.01). A similar discrepancy for itraconazole was not significant (P > 0.5). We did not observe differences in fluconazole or itraconazole susceptibility profiles among C. glabrata isolates associated with either hematogenous dissemination or colonization. The significant discrepancy in antifungal susceptibility among C. glabrata organisms isolated from hospitals in the same geographic region emphasizes the significance of periodic susceptibility surveillance programs for individual institutions, especially those providing care to patients at risk.     

In vitro activities of lomefloxacin, tetracycline, penicillin, spectinomycin, and ceftriaxone against Neisseria gonorrhoeae and Chlamydia trachomatis.

In vitro lomefloxacin was highly active against 208 penicillin-susceptible and -resistant isolates of Neisseria gonorrhoeae. However, its MIC and MBC against 10 isolates of Chlamydia trachomatis were 2 and greater than 4 micrograms/ml, respectively.     

Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men

OBJECTIVES: A validated microbiological assay was used to measure concentrations of iclaprim (AR-100) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF) after a single 1.6 mg/kg intravenous 60 min iv infusion of iclaprim. METHODS: Male volunteers were randomly allocated to three nominal sampling time intervals 1-2 h (Group A), 3-4 h (Group B) and 5.5-7.0 h (Group C) after the start of the drug infusion. RESULTS: Mean iclaprim concentrations in plasma, BM, AM and ELF, respectively, were for Group A 0.59 mg/L (SD 0.18), 0.51 mg/kg (SD 0.17), 24.51 mg/L (SD 21.22) and 12.61 mg/L (SD 7.33); Group B 0.24 mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38 mg/L (SD 5.17); and Group C 0.14 mg/L (SD 0.05), no detectable level in BM, 5.28 mg/L (SD 2.30) and 2.66 mg/L (SD 2.08). CONCLUSIONS: Iclaprim concentrations in ELF and AM exceeded the MIC(90) for penicillin-susceptible Streptococcus pneumoniae (MIC90 0.06 mg/L), penicillin-intermediate S. pneumoniae (MIC90 2 mg/L), penicillin-resistant S. pneumoniae (MIC90 4 mg/L) for 7, 7 and 4 h, respectively, and Chlamydia pneumoniae (MIC90 0.5 mg/L) for 7 h. Mean iclaprim concentrations in ELF exceeded the MIC90 for Haemophilus influenzae (MIC90 4 mg/L) and Moraxella catarrhalis (MIC90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC90 was exceeded for up to 7 h. Furthermore, the MIC90 for methicillin-resistant Staphylococcus aureus of 0.12 mg/L was exceeded at all sites for up to 7 h. These data suggest that iclaprim reaches lung concentrations that should be effective in the treatment of community-acquired pneumonia.