In vitro activities of azithromycin, clarithromycin, erythromycin, and tetracycline against 13 strains of Chlamydia pneumoniae.

Thirteen strains of Chlamydia pneumoniae were evaluated for their in vitro susceptibilities to azithromycin, clarithromycin, erythromycin, and tetracycline. The MIC ranges were 0.125 to 0.5 micrograms/ml for azithromycin, 0.031 to 1.0 micrograms/ml for clarithromycin, 0.125 to 1.0 micrograms/ml for erythromycin, and 0.25 to 1.0 micrograms/ml for tetracycline. The ranges for the minimal lethal concentrations were 0.125 to 0.5 micrograms/ml for azithromycin, 0.031 to 1.0 micrograms/ml for clarithromycin, 0.125 to 1.0 micrograms/ml for erythromycin, and 0.25 to 1.0 micrograms/ml for tetracycline. Clarithromycin and azithromycin were the most active antibiotics against C. pneumoniae in vitro.     

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 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.     

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.     

Chlamydia trachomatis: in vitro susceptibility of genital and ocular isolates to some quinolones, amoxicillin and azithromycin

The minimum inhibitory concentration (MIC) of ofloxacin, ciprofloxacin, norfloxacin, amoxicillin and a new erythromycin analogue (azithromycin or CP 62993) against Chlamydia trachomatis was determined. There was a large difference between the MICs (microgram/ml) of different quinolones (median of 3 independent measurements; range): ofloxacin (0.5; 0.5-1) less than ciprofloxacin (1; 1-2) less than norfloxacin (16; 16-32). The MIC of amoxicillin varied from 0.25 to 1 (median 0.5) in different experiments. The MIC of azithromycin (0.125; 0.063-0.25) was lower than that of erythromycin (0.25; 0.125-0.5). The minimum lethal concentration (MLC) of ofloxacin and azithromycin was determined with and without passage of the McCoy cells. Both methods gave the same results. Ofloxacin seemed to have a lethal effect on C. trachomatis, as the MIC and MLC were equal. In contrast, the effect of the MIC of azithromycin on C. trachomatis was bacteriostatic. The MLC of azithromycin was 2-4 times higher than the MIC (p less than 0.001).     

Susceptibilities of Chlamydia trachomatis isolates causing uncomplicated female genital tract infections and pelvic inflammatory disease.

The in vitro susceptibilities of 45 recent clinical isolates of Chlamydia trachomatis obtained from women with asymptomatic genital tract infection, mucopurulent cervicitis, or pelvic inflammatory disease to doxycycline, azithromycin, ofloxacin, and clindamycin were determined. In addition, susceptibilities of 12 isolates to amoxicillin and trimethoprim-sulfamethoxazole were also determined. Isolates also were serotyped with a panel of monoclonal antibodies specific for chlamydial major outer membrane protein; 24 of 45 (53%) belonged to serovars Ia and E. For all isolates, the MIC range of doxycycline was 0.008 to 0.06 micrograms/ml, for trimethoprim-sulfamethoxazole it was 0.03 to 0.25 micrograms/ml, for azithromycin it was 0.125 to 2.0 micrograms/ml, for ofloxacin it was 0.5 to 1.0 micrograms/ml, for clindamycin it was 0.25 to 2.0 micrograms/ml, and for amoxicillin it was 0.25 to 4.0 microgram/ml. The ranges of minimum chlamydiacidal concentrations were generally 1 to 4 dilutions above the MICs of most agents, with a rank order similar to those of the MICs. Comparing the minimum chlamydiacidal concentrations for 90% of isolates tested, isolates causing asymptomatic infection belonged to a greater variety of serovars and were relatively more susceptible to doxycycline and azithromycin than isolates causing mucopurulent cervicitis or pelvic inflammatory disease; these differences in susceptibility were not detected among the other study agents. These data indicate that additional studies are needed to better define the apparent association of certain chlamydial serovars with the clinical severity of disease and the in vitro susceptibilities to certain antimicrobial agents.     

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.     

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

The in vitro susceptibilities of 11 strains of Chlamydia pneumoniae to azithromycin, clarithromycin, erythromycin, L-oflaxacin, and doxycycline were determined. Clarithromycin was the most active agent tested, with an MIC for 90% of strains and minimal chlamydiacidal concentration for 90% of strains of 0.03 microns/ml. The activity of azithromycin was similar to those of erythromycin and doxycycline, with MICs for 90% of strains of 0.125 to 0.25 microns/ml. However, the prolonged half-life and enhanced tissue penetration of azithromycin should allow for less frequent dosing and shorter duration of therapy than with erythromycin or clarithromycin. L-Ofloxacin had activity similar to that of ofloxacin, with MICs of 0.125 to 0.5 micron/ml. From the results of this in vitro study, azithromycin and clarithromycin appear to be effective antibiotics that may have a role in the treatment of infections due to C. pneumoniae.     

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 evaluation of CP-62,993, erythromycin, clindamycin, and tetracycline against Chlamydia trachomatis.

The antimicrobial activity of CP-62,993 against four Chlamydia trachomatis isolates was compared with those of erythromycin, clindamycin, and tetracycline. The MIC of CP-62,993 was 0.26 to 1.02 micrograms/ml for 100% inclusion inhibition and 0.031 to 0.063 microgram/ml for 50% inclusion inhibition. With pharmacokinetic and antimicrobial studies demonstrating prolonged half-life and in vitro effectiveness, CP-62,993 may make possible a single, short-course treatment regimen for C. trachomatis infection.     

Susceptibility of Mycoplasma pneumoniae to several new quinolones, tetracycline, and erythromycin.

Mycoplasma pneumoniae (39 strains) was most susceptible to two quinolones, WIN 57273 and sparfloxacin, with MICs for 90% of the strains (MIC90S) of 0.125 and 0.25 micrograms/ml, respectively. It was susceptible to ofloxacin and ciprofloxacin at 2 micrograms/ml and to lomefloxacin and fleroxacin at 4 micrograms/ml. The MIC90 of erythromycin was 0.062 microgram/ml, and that of tetracycline was 1 microgram/ml.     

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.     

In vitro antimicrobial activity of rosoxacin against Neisseria gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum.

The antimicrobial activity of rosoxacin, a new quinoline antibacterial compound, was determined against the causative organisms of three sexually transmitted diseases. Rosoxacin demonstrated a high degree of activity against Neisseria gonorrhoeae clinical isolates, with the minimal inhibitory concentrations for 50% of these being 0.03 microgram/ml. The corresponding minimal inhibitory concentrations for penicillin, ampicillin, tetracycline, and spectinomycin were 0.25 U/ml, 0.125 microgram/ml, 0.25 microgram/ml, and 16 microgram/ml, respectively. Eleven strains of Chlamydia trachomatis were inhibited by 5 microgram of rosoxacin per ml, and each of seven Ureaplasma urealyticum strains was inhibited by 2 to 8 microgram of rosoxacin per ml. The results of these susceptibility studies, coupled with those of an earlier evaluation of the pharmacokinetics of rosoxacin, provide support for extending or undertaking clinical evaluations of this compound against infections with N. gonorrhoeae, C. trachomatis, and U. urealyticum.     

Relative resistance to erythromycin in Chlamydia trachomatis.

Recent Chlamydia trachomatis isolates were tested in a tissue culture system for susceptibility to tetracycline, erythromycin, rosaramicin, rifampin, and clindamycin. Rifampin was the most active drug (minimal inhibitory concentration, less than or equal to 0.02 microgram/ml). Tetracycline and rasaramicin were highly active, with a concentration of less than or equal to 0.25 microgram/ml being chlamydicidal. Clindamycin was least active on a weight basis, requiring up to 16 microgram/ml to prevent the passage of chlamydiae into a drug-free tissue culture system. Relative resistance to erythromycin was detected; two isolates were capable of limited replication in 1 microgram/ml.     

In vitro susceptibilities of isolates of Haemophilus ducreyi from Thailand and the United States to currently recommended and newer agents for treatment of chancroid.

We determined the in vitro susceptibilities of 54 isolates of Haemophilus ducreyi from Thailand (29 isolates) and San Francisco (25 isolates) to penicillin G, tetracycline, amoxicillin-clavulanic acid, ceftriaxone, cefixime, erythromycin, azithromycin, ciprofloxacin, ofloxacin, and trimethoprim-sulfamethoxazole. Isolates were susceptible to < or = 0.25 microgram of ceftriaxone per ml, < or less 0.5 microgram of cefixime per ml, < or = 0.125 microgram of ciprofloxacin per ml, and < or = 0.06 microgram of ofloxacin per ml. Erythromycin was active against all isolates (MIC for 90% of isolates tested, 0.25 microgram/ml), as was azithromycin (MIC, < or = micrograms/ml). In contrast, all but one isolate were resistant to > or = 8.0 micrograms of tetracycline per ml, 11.1% of the isolates were resistant to and 40.9% of the isolates were resistant to trimethoprim-sulfamethoxazole (MIC, > or = 4/76 microgram/ml.)     

Protective effects of sparfloxacin in experimental pneumonia caused by Chlamydia pneumoniae in leukopenic mice.

The in vivo antichlamydial activities of sparfloxacin and reference drugs were examined in a experimental model of pneumonia caused by Chlamydia pneumoniae in leukopenic mice; their in vitro activities were also examined. The most potent agents in vitro were sparfloxacin (MICs for C. pneumoniae Kajaani and IOL 207, (0.031 and 0.031 micrograms/ml, respectively), clarithromycin (0.031 and 0.031 micrograms/ml, respectively), and minocycline (0.031 and 0.031 micrograms/ml, respectively); these were followed by tosufloxacin (0.063 and 0.125 micrograms/ml, respectively) and ofloxacin (0.5 and 0.5 micrograms/ml, respectively). The MBCs of sparfloxacin, tosufloxacin, ofloxacin, clarithromycin, and minocycline for these two strains were 0.063 and 0.063 micrograms/ml, 0.125 and 0.25 micrograms/ml, 1.0 and 1.0 micrograms/ml, 0.125 and 0.125 micrograms/ml, and 0.25 and 0.25 micrograms/ml, respectively. Fatal pneumonia was induced by intranasal inoculation of cyclophosphamide-treated leukopenic mice with C. pneumoniae IOL 207; infiltration of neutrophils and lymphocytes was observed in the lungs of these mice by histopathological examination. The 50% effective dose of sparfloxacin (oral dose of 0.97 mg/kg of body weight) against the pneumonia was the lowest among the drugs tested; this was followed by those of minocycline (2.22 mg/kg), tosufloxacin (3.47 mg/kg), clarithromycin (4.66 mg/kg), and ofloxacin (16.6 mg/kg). The results indicate that it may be worthwhile to use sparfloxacin against C. pneumoniae infections in humans.     

In vitro activity of sparfloxacin and other antimicrobial agents against genital pathogens.

The in vitro activity of sparfloxacin was determined for 60 strains of Neisseria gonorrhoeae, 15 strains of Chlamydia trachomatis and 40 strains each of Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ampicillin, azithromycin, clarithromycin, erythromycin, ofloxacin, temafloxacin and tetracycline. Sparfloxacin was active against all the strains studied and appeared to be the most potent quinolone tested. Sparfloxacin had the lowest MICs against N. gonorrhoeae (MICs 0.002-0.06 micrograms/ml). Its MICs against C. trachomatis (0.03-0.06 micrograms/ml) were higher than those of clarithromycin but lower than those of the other antimicrobial agents. Sparfloxacin was particularly active against tetracycline-susceptible as well as resistant strains of M. hominis (MICs, 0.06 micrograms/ml) and U. urealyticum (MICs 0.125-1 micrograms/ml). Because of this in vitro activity and its tissue distribution, sparfloxacin might be a valuable therapeutic agent for treating major bacterial sexually transmitted diseases.     

In vitro susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to sparfloxacin and PD 127391.

The in vitro activities of two investigational quinolones, sparfloxacin (previously designated AT 4140) and PD 127391, were determined for 30 strains each of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ciprofloxacin, tetracycline, clindamycin, and erythromycin. Erythromycin was the most active compound against M. pneumoniae (maximum MIC, less than 0.008 microgram/ml). PD 127391 (MICs, less than 0.008 to 0.031 microgram/ml), sparfloxacin (MICs, less than 0.008 to 0.25 microgram/ml), clindamycin (MICs, less than 0.008 to 0.5 microgram/ml), and tetracycline (MICs, 0.063 to 0.25 microgram/ml) were superior to ciprofloxacin (MICs, 0.5 to 2 microgram/ml). Sparfloxacin and PD 127391 were active against M. hominis (MICs, less than 0.008 to 0.031 microgram/ml for each) at concentrations comparable to those of clindamycin (MICs, less than 0.008 to 0.063 microgram/ml) and at concentrations lower than those of ciprofloxacin (MICs, 0.125 to 0.5 microgram/ml). As expected, M. hominis was resistant to erythromycin (MICs, 32 to greater than or equal to 256 micrograms/ml). For U. urealyticum, PD 127391 (MICs, 0.031 to 0.5 microgram/ml) and sparfloxacin (MICs, 0.063 to 1 microgram/ml) were superior to erythromycin (MICs, 0.25 to 4 micrograms/ml), ciprofloxacin (MICs, 0.5 to 8 micrograms/ml), and clindamycin (MICs, 0.25 to 64 micrograms/ml. Both new quinolones were equally active against tetracycline-susceptible as well as resistant strains of M. hominis and U. urealyticum. The possible influence of medium components and/or pH on MICs was evaluated by testing a Staphylococcus aureus reference strain with each antibiotic in SP-4 broth and 10-B broth and comparing the results with published MICs for this strain. MICs determined in 10-B broth for erythromycin were affected most. This study shows that the activities of sparfloxacin and PD 127391 are similar to one another and comparable or superior to those of other drugs used to treat mycoplasmal infections. The MICs of both new quinolones were consistently 2 to several dilutions lower than those of ciprofloxacin for each species.     

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 activities of two glycylcyclines.

The in vitro activities of two glycylcyclines, CL 329,998 and CL 331,002 (two new semisynthetic tetracyclines), were evaluated in comparison with those of tetracycline and other available oral antimicrobial agents. A total of 523 recent clinical isolates were studied, including strains resistant to tetracycline. Members of the family Enterobacteriaceae were generally > or = 16-fold more susceptible to the glycylcyclines than to tetracycline (although less difference was seen with Proteus spp.). Pseudomonas aeruginosa was modestly susceptible to both new compounds (MIC for 90% of strains tested [MIC90], 16 micrograms/ml). Tetracycline- and methicillin-susceptible and -resistant strains of Staphylococcus aureus were all susceptible to the glycylcyclines (MIC90 < or = 1 microgram/ml). Streptococci (including Streptococcus pneumoniae) and Enterococcus faecalis and Enterococcus faecium displayed a bimodal distribution of susceptibility to tetracycline yet were uniformly susceptible to the glycylcyclines (MIC90 < or = 0.25 microgram/ml). The glycylcyclines were highly potent against Neisseria, Moraxella, Haemophilus, and Bacteroides spp. (MIC90 < or = 0.5 microgram/ml). Strains of Chlamydia spp. (three C. trachomatis strains and one C. pneumoniae strain) were inhibited by < or = 0.25 microgram of CL 329,998 or CL 331,002 per ml. Two strains of Mycoplasma pneumoniae were inhibited by < or = 0.12 microgram of CL 331,002 per ml and by 1 microgram of CL 329,998 per ml. Mycobacterium tuberculosis and Mycobacterium avium were resistant to the two glycylcyclines (MIC > or = 8 micrograms/ml). These results indicate that the two glycylcyclines have potent in vitro activities against a wide range of clinically important pathogenic bacteria.