In vitro antibacterial activity of Q-35, a new fluoroquinolone.

The in vitro activity of Q-35, an 8-methoxy fluoroquinolone, was compared with those of ofloxacin, ciprofloxacin, tosufloxacin, lomefloxacin, and sparfloxacin. The MICs of Q-35 for 90% of strains tested (MIC90s) of Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Streptococcus pyogenes were 0.2, 6.25, 0.2, 0.39, and 0.39 micrograms/ml, respectively. The activity of Q-35 was 4- to 16-fold greater than those of ofloxacin, ciprofloxacin and lomefloxacin but equal to those of tosufloxacin and sparfloxacin against these organisms. For 82 ciprofloxacin-resistant staphylococci (MIC90 = 100 micrograms/ml), Q-35 was the most active of the new quinolones tested (MIC90 = 6.25 micrograms/ml). The MIC90s of Q-35 against Escherichia coli, Enterobacter aerogenes, and Pseudomonas aeruginosa were 0.2, 0.78, and 12.5 micrograms/ml, respectively, and Q-35 was 2- to 16-fold less active than the other quinolones tested. Q-35 showed potent bactericidal activity and inhibited the supercoiling activity of DNA gyrase of S. aureus, E. coli, and P. aeruginosa.     

Improved bactericidal activity of Q-35 against quinolone-resistant staphylococci.

The bactericidal effects of Q-35, sparfloxacin, tosufloxacin, and ofloxacin on 18 strains of methicillin-resistant Staphylococcus aureus (MRSA) and 3 strains of Staphylococcus epidermidis were studied by a viable-count method. Staphylococci as used in this study were clearly divided into two groups with respect to their susceptibilities to sparfloxacin. MICs of Q-35 and tosufloxacin were 0.05 to 0.78 microgram/ml for sparfloxacin-susceptible strains (MICs, 0.05 to 0.2 microgram/ml) and 1.56 to 12.5 micrograms/ml for sparfloxacin-resistant strains (6.25 to 25 micrograms/ml). All the sparfloxacin-resistant strains of MRSA tested contained the gyrA mutation at codon 84. Time-kill studies showed that Q-35 decreased the viable counts from approximately 10(7) CFU/ml to 10(3) to 10(5) CFU/ml within 3 h at concentrations greater than the MICs against both sparfloxacin-susceptible and -resistant strains. In contrast, sparfloxacin, tosufloxacin, and ofloxacin produced bacteriostatic effects at 3 h after exposure against sparfloxacin-resistant strains at concentrations which were greater than the respective MICs, whereas these quinolones were bactericidal against sparfloxacin-susceptible strains. The rapid bactericidal activities of Q-35 against sparfloxacin-resistant MRSA were reduced when the methoxy group of Q-35 at the 8 position was substituted with fluorine or hydrogen. Thus, our data suggest that the introduction of a methoxy group into the 8 position of quinolones contributes to the bactericidal activities of fluoroquinolones against quinolone-resistant staphylococci.     

In vitro and in vivo activities of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae.

The in vitro potency and in vivo efficacy of Q-35, a new fluoroquinolone, against Mycoplasma pneumoniae were investigated by pharmacokinetic studies with M. pneumoniae-infected hamsters. By using fluoroquinolones, macrolides, and tetracyclines as references, Q-35 was found to possess the greatest mycoplasmacidal activity. The MIC for 90% of strains tested (MIC90) and the MIC50 were 0.78 and 0.39 microgram/ml, respectively, and the MBC for 90% of strains tested (MBC90) and the MBC50 were 3.13 and 0.78 microgram/ml, respectively. The MBC50-to-MIC50 ratio for Q-35 was 2. Furthermore, only Q-35 continued to be effective against 19 strains of erythromycin-resistant mutants of M. pneumoniae. The efficacies of fluoroquinolones against M. pneumoniae were also investigated by using an experimental hamster pneumonia model to measure the CFU of M. pneumoniae in the lungs. Q-35 and ofloxacin were efficacious following oral administration of 200 mg/kg/day for 5 days, initiated 24 h after infection, while ciprofloxacin was not active. Continuous administration of Q-35 for 10 days significantly reduced numbers of viable M. pneumoniae in the lungs. These results suggest that both Q-35 and ofloxacin are effective in the early phase of infection and, moreover, that Q-35 is also effective in the middle stage of infection, when progressive lung alterations and continuous increases in mycoplasmal growth occur. Peak levels of Q-35 in sera and lungs after oral administration were higher than those of ciprofloxacin but lower than those of ofloxacin. On the basis of these results, Q-35 appears to be a promising antimicrobial agent in chemotherapy of mycoplasmal infection.     

In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci.

The in vitro activity of RP 59500, a semisynthetic pristinamycin, was compared with the activities of vancomycin, oxacillin, ampicillin, gentamicin, ciprofloxacin, and rifampin against five Staphylococcus species, five Streptococcus species, and four Enterococcus species. For staphylococci, MICs were 0.13 to 1 microgram/ml and the MICs for 90% of the strains tested (MIC90s) were 0.13 to 0.5 microgram/ml; there were no differences between oxacillin-susceptible and -resistant strains. For streptococci, MICs were 0.03 to 4 micrograms/ml and MIC90s were 0.25 to 2 micrograms/ml; viridans group streptococci were the least susceptible streptococci. For enterococci, MICs were 0.25 to 32 micrograms/ml and MIC90s were 2 to 4 micrograms/ml; Enterococcus faecalis was the least susceptible. Vancomycin was the only comparative drug with consistent activity against all species of gram-positive cocci. With RP 59500, raising the inoculum 100-fold, lowering the pH of cation-adjusted Mueller-Hinton broth to 5.5, or omitting cation supplementation had little effect on MICs, but 50% serum increased MICs 2 to 4 dilution steps. The differences between MBCs and MICs were greater for staphylococci and enterococci than for streptococci. Time-kill studies with 24 strains indicated that RP 59500 concentrations 2-, 4-, and 16-fold greater than the MICs usually killed bacteria of each species at similar rates; reductions in CFU per milliliter were less than those observed with oxacillin or vancomycin against staphylococci and less than those observed with ampicillin against enterococci. RP 59500 antagonized the bactericidal activities of oxacillin and gentamicin against Staphylococcus aureus ATCC 29213 and that of ampicillin against E. faecalis ATCC 29212. Against the latter, combination with gentamicin was indifferent. RP 59500 has a broad spectrum of in vitro activity against gram-positive cocci; combining it with other drugs is not advantageous.     

In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts

The in vitro activity of the novel triazole antifungal agent posaconazole (Noxafil; SCH 56592) was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC(50) and MIC(90) values for posaconazole were 0.063 microg/ml and 1 mug/ml, respectively. MIC(90) values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 mug/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.     

Comparative in vitro activities of caspofungin and micafungin, determined using the method of the European Committee on Antimicrobial Susceptibility Testing, against yeast isolates obtained in France in 2005-2006

The in vitro activities of caspofungin and micafungin against 1,038 yeast isolates have been determined. The caspofungin and micafungin MICs were lower for Candida albicans, Candida glabrata, and Candida tropicalis than for Candida parapsilosis, Candida guilliermondii, and Candida krusei. A clear correlation was seen between the MICs for the two drugs.     

Comparative in vitro activity of five cathelicidin-derived synthetic peptides against Leptospira,Borrelia and Treponema pallidum

OBJECTIVE: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of five different cathelicidin-derived synthetic peptides (SMAP-29, LL-37, PG-1, CRAMP and BMAP-28) for Leptospira interrogans, Borrelia spp. and Treponema pallidum subsp. pallidum were investigated in vitro. METHODS: The MIC of individual peptides was defined as the lowest concentration able to inhibit the motility of spirochaetes after 2 h of incubation, as detected by dark-field microscopy. The MBC of individual peptides was defined as the lowest concentration at which no spirochaetes were subcultured either in cathelicidin-free medium (leptospires and borreliae) or in hamsters (T. pallidum). RESULTS: The MIC values of peptides for leptospires were highly variable, depending on the compound and the strain used. Of the five cathelicidin-derived peptides, SMAP-29 from sheep and BMAP-28 from cattle were the most active against L. interrogans serovars, with MIC values varying between 3 and 51 mg/L, depending on the strains. The MICs of the remaining synthetic peptides ranged between 4.3 and 224 mg/L. The MIC values of synthetic peptides for T. pallidum ranged between 32.3 mg/L for PG-1 and 449.4 mg/L for LL-37. The MICs of all cathelicidin-derived peptides tested for Borrelia strains ranged between 307 and 449.4 mg/L. The activity of the peptides on the motility of spirochaetes was both dose- and time-dependent. The MBC values of the peptides were the same as the MIC values. CONCLUSION: The results of this study demonstrate that the activity of cathelicidin-derived peptides against spirochaetes is fast and highly variable, depending on the species and the strain.     

Broth microdilution susceptibility testing for Leptospira spp

Leptospirosis in humans has traditionally been treated with penicillin or doxycycline. The choice of therapy offered at the time of initial patient presentation is often empirical, as definitive diagnosis can take weeks. Determining the activity of numerous antimicrobial agents against a wide range of Leptospira serovars may broaden empirical therapeutic options. Various antimicrobials have been shown to be active against a limited number of serovars in in vitro studies, chiefly by the use of broth macrodilution techniques. We developed a broth microdilution technique using the commercially available growth indicator alamarBlue. MICs produced by this technique were compared to MICs and minimal bactericidal concentrations produced by the traditional broth macrodilution technique. The internal validity of our methods was assessed with 11 runs over numerous days with a single isolate of Leptospira interrogans serovar Icterohaemorrhagiae. By either method, the MICs for these internal-validity runs fell within 2 dilutions of each other for more than 90% of antimicrobials. A broader application of these two techniques included 12 serovars (including seven species) of Leptospira and six antimicrobials (penicillin G, doxycycline, chloramphenicol, erythromycin, cefotaxime, and ciprofloxacin). Observed reproducibility fell within 2 dilutions for 99% of the duplicate result sets for the MIC microdilution method, compared to 89% for the MIC macrodilution method. The macrodilution method tended to have a higher MIC at which 90% of the isolates were inhibited (MIC(90)) than did the microdilution method, but the MIC(90)s of both methods were within 2 dilutions of each other for all six drugs. The macrodilution and microdilution techniques produced similar results, with microdilution allowing a faster, more streamlined method of producing MIC results.     

Comparison of bactericidal activities of streptomycin, amikacin, kanamycin, and capreomycin against Mycobacterium avium and M. tuberculosis.

The bactericidal activities of four injectable antituberculosis drugs, streptomycin, amikacin, kanamycin, and capreomycin, against Mycobacterium avium and M. tuberculosis were tested. All four drugs were highly bactericidal against M. tuberculosis, with low MBC/MIC ratios and MBCs significantly lower than the maximum achievalbe concentrations in serum (Cmax). In contrast, all four drugs had very low bactericidal activities against M. avium: the broth-determined MBCs were significantly higher than the Cmax. On a basis of comparisons with the broth-determined MICs found for susceptible M. tuberculosis strains and with the Cmax, about one-third of 100 M. avium strains tested can be tentatively considered as susceptible to three aminoglycosides (streptomycin, amikacin, and kanamycin) but not to capreomycin. In regard to the MBCs and MICs, the three aminoglycosides tested have about identical potentials as drugs of choice in combination with other drugs for chemotherapy of M. avium disease. The low bactericidal activities of these drugs against M. avium in vitro do not exclude their therapeutic usefulness, because they may produce a synergistic effect in combination with other drugs. Such an option is especially promising for patients whose isolates can be considered susceptible on the basis of the MIC. We found no differences in susceptibility to the four drugs tested for M. avium strains (identified by Gen-Probe) isolated from 50 patients with and 50 patients without acquired immune deficiency syndrome.     

Antipneumococcal activity of AZD2563, a new oxazolidinone,compared with nine other agents

The in vitro activity of AZD2563, a new oxazolidinone, was compared with that of linezolid, vancomycin, quinupristin/dalfopristin, amoxicillin, levofloxacin, penicillin, erythromycin, azithromycin and clindamycin against a range of pneumococci by microdilution and time-kill studies. Against 300 pneumococci (99 penicillin susceptible, 86 penicillin intermediate, 115 penicillin resistant, 185 erythromycin resistant, 35 quinolone resistant), both oxazolidinones remained active against isolates less susceptible to other agents, with MICs ranging between 0.125 and 2 mg/L; AZD2563 MICs were generally one dilution lower than those of linezolid. Both quinupristin/dalfopristin and vancomycin were active against all groups (MIC ranges 0.125-2 and 0.125-0.25 mg/L, respectively). Apart from 35 isolates with levofloxacin MICs > or= 8 mg/L, levofloxacin MICs were < or =0.25-4 mg/L. MICs of amoxicillin and erythromycin rose with penicillin G MICs; most macrolide-resistant isolates were either penicillin-intermediate or -resistant. Against 16 organisms with differing beta-lactam, macrolide and quinolone MICs, time-kill studies showed that AZD2563 was bactericidal (99.9% killing) at 4 x MIC against nine strains at 24 h, with 90% killing of all 16 strains at 2 x MIC after 12 h. Similar results were obtained with linezolid. Both oxazolidinones were bacteriostatic at the MIC against all 16 strains. Amoxicillin, levofloxacin and vancomycin, at 2 x MIC, were bactericidal against 15 of the 16 strains after 24 h. Quinupristin/dalfopristin yielded the most rapid killing, with bactericidal activity against 13 of 16 strains at the MIC after 3 h and against 15 strains at 2 x MIC after 24 h. Erythromycin was bactericidal against all 10 strains with MICs < or= 8 mg/L at 4 x MIC after 24 h.     

In vitro activities of pentamidine,pyrimethamine, trimethoprim,and sulfonamides against Aspergillus species

The susceptibilities of 70 strains of Aspergillus species were tested against seven different sulfa drugs and pentamidine by a microdilution method with RPMI 1640 and yeast nitrogen base media. Sulfamethoxazole, sulfadiazine, and pentamidine were active in vitro. The MICs obtained with RPMI 1640 were significantly higher than those with yeast nitrogen base. More studies are needed to further elucidate the action of these drugs.     

In vitro and in vivo antibacterial activities of MT-141, a new semisynthetic cephamycin, compared with those of five cephalosporins.

The in vitro and in vivo antibacterial activities of MT-141 were compared with those of cefoxitin, cefmetazole, moxalactam, cefotaxime, and cefoperazone. The MICs of MT-141 for 90% of bacterial isolates were lower than the reference drugs against clinical isolates of Campylobacter jejuni, Clostridium difficile, and Bacteroides fragilis, whereas against clinical isolates of other gram-positive, gram-negative, and anaerobic bacteria, the MICs of MT-141 were similar to or higher than those of the reference drugs. In contrast, the bactericidal activity of MT-141 after 6- and 24-h exposures was superior to all of the reference drugs against 9 to 10 of the 12 bacterial strains studied, including Escherichia coli, Klebsiella pneumoniae, Salmonella enteritidis, indol-positive Proteus species, Serratia marcescens, Yersinia enterocolitica, Pseudomonas cepacia, and Clostridium perfringens. In the treatment of systemic infections in mice, MT-141 was again superior against 9 of the 12 strains tested, showing a good correlation with the bactericidal activity. It was found that the 50% effective doses of the six cephalosporins studied correlated better with the MBCs than with the MICs. As the serum levels of MT-141 in mice after subcutaneous administration were similar to those of the reference drugs, it was concluded that the bactericidal activity of MT-141 was a dominant factor in its in vivo activity.     

Activities of roxithromycin used alone and in combination with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine against Mycobacterium avium complex.

Preliminary studies showed that roxithromycin possessed significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii and rare pathogens such as M. chelonae and M. fortuitum. In this investigation, radiometric MICs of roxithromycin, ethambutol, rifampin, amikacin, ofloxacin, and clofazimine for 10 clinical isolates of the M. avium complex (5 each from human immunodeficiency virus [HIV]-positive and HIV-negative patients) were determined. Roxithromycin MICs against all the isolates were below the reported maximum concentration of drug in serum at the routine pH of 6.8, and the MICs were further lowered by 1 to 2 dilutions at a pH of 7.4. In vitro enhancement of roxithromycin activity against all strains was further investigated by the previously established Bactec 460-TB method by combining the drugs at sub-MIC levels. Antibacterial activity of roxithromycin was enhanced in all 10 strains by ethambutol, in 3 strains each by rifampin and clofazimine, in 2 strains by amikacin, and in 1 strain by ofloxacin. In vitro screening of three-drug combinations showed that combinations of roxithromycin, ethambutol, and a third potential anti-M. avium drug (rifampin, amikacin, ofloxacin, or clofazimine) resulted in further enhancement of activity in 13 out of 20 drug combinations screened.     

In vitro activities of daptomycin, vancomycin, and penicillin against Clostridium difficile, C. perfringens, Finegoldia magna, and Propionibacterium acnes

Daptomycin has in vitro activity against gram-positive anaerobic bacteria, although limited numbers of species have been tested. We studied the in vitro activities of daptomycin, vancomycin, and penicillin against more than 100 strains each of Clostridium difficile, C. perfringens, Finegoldia magna, and Propionibacterium acnes. Daptomycin Etest MICs and results from time-kill studies were determined for selected strains. For 392 of 421 strains (93%), daptomycin was inhibitory at < or =1 microg/ml, including 15 of 16 strains of C. difficile with elevated linezolid MICs of 8 and 16 microg/ml, all 32 strains with moxifloxacin MICs of > or =4 microg/ml, and all 16 strains resistant to clindamycin. Daptomycin MICs were also < or =1 microg/ml for all 16 F. magna strains resistant to clindamycin and all 32 strains resistant to tetracycline. Only one strain, a C. perfringens strain, had a MIC of >2 microg/ml to daptomycin. Eighty-five and 92.5% of the Etest MICs were within 1 dilution of the agar dilution method for all drugs at 24 and 48 h, respectively. In time-kill studies, a C. difficile strain was inhibited by both daptomycin and vancomycin at 1, 2, 4, 8, and 24 h; colony counts were decreased by 2.3 to 2.9 log at 24 h. Vancomycin was not bactericidal for C. perfringens; however, daptomycin showed bactericidal activity as early as 1 h at four and eight times the MIC and at 2 and 4 h at two and four times the MIC.     

Activities of vancomycin and teicoplanin against penicillin-resistant pneumococci in vitro and in vivo and correlation to pharmacokinetic parameters in the mouse peritonitis model.

The activities of glycopeptides against pneumococci were studied in vitro and in vivo. The MICs of two glycopeptides, vancomycin and teicoplanin, in different media against 10 strains of pneumococci with different susceptibilities to penicillin were determined. The MICs of teicoplanin were four times lower than those of vancomycin in Mueller-Hinton media supplemented with 5% blood, but the MICs were similar in mouse and human sera supplemented with 5% blood. The serum protein binding levels in mouse and human sera were 90% for teicoplanin in both and 25 and 35%, respectively, for vancomycin. The MICs for vancomycin and teicoplanin were only correlated in human serum (P < 0.001). The single doses giving protection to 50% of the animals in the mouse peritonitis model after a lethal challenge of pneumococci, the ED50s, were similar for vancomycin and teicoplanin, between 0.1 and 1 mg/kg of body weight for all 10 strains. The log ED50s were significantly correlated only to the log MICs of teicoplanin determined for mouse serum with 5% blood (P = 0.01) and to the log MICs of vancomycin determined by the E test (P = 0.03). Among the pharmacokinetic parameters analyzed at the ED50s, the most constant parameter was the time for which the drug concentration exceeded the MIC (T(>MIC)) when each drug was considered separately; however, when both drugs were considered together, the maximum concentration of drug in serum (Cmax) varied the least. This indicates that both these parameters are of importance for predicting the effect of the drugs. We conclude that the effect of glycopeptides was not influenced by the penicillin resistance of the pneumococci, either in vitro or in vivo, and that the superior activity of teicoplanin over that of vancomycin in vitro was abolished in vivo, an effect which probably was due to the high serum protein binding of teicoplanin. Both the pharmacokinetic parameters T(>MIC) and Cmax are important predicting the effect of glycopeptides, but the pharmacodynamics of glycopeptides are still not completely elucidated.     

Susceptibilities to clarithromycin and erythromycin of isolates of Chlamydia pneumoniae from children with pneumonia.

We tested in vitro 49 isolates of Chlamydia pneumoniae obtained from 35 children with community-acquired pneumonia against clarithromycin and erythromycin. The children were part of a treatment study comparing the two drugs. Clarithromycin was 2- to 10-fold more active than erythromycin, with a MIC for 90% of strains tested and minimal chlamydiacidal concentration for 90% of strains tested of 0.031 microgram/ml compared with 0.125 microgram/ml for erythromycin. Eight of these children, two of whom were treated with erythromycin and six of whom received clarithromycin, remained culture positive after treatment. We were able to test 21 isolates from these children. All were susceptible to both drugs, and the MICs did not change after therapy.     

In vitro anti-Helicobacter pylori activities of new rifamycin derivatives, KRM-1648 and KRM-1657

The new rifamycin derivatives KRM-1657 and KRM-1648 were evaluated for their in vitro antimicrobial activities against 44 strains of Helicobacter pylori. Although the drugs were not very active against other gram-negative bacteria, the MICs at which 90% of isolates are inhibited for these drugs were lower (0.002 and 0.008 microgram/ml, respectively) than those of amoxicillin and rifampin for H. pylori. Time-kill studies revealed that the bactericidal activities of these agents were due to cell lysis. The results presented here indicate that these new rifamycin derivatives may be useful for the eradication of H. pylori infections.     

Comparative in vitro activities of teicoplanin, daptomycin, ramoplanin, vancomycin, and PD127,391 against blood isolates of gram-positive cocci.

The in vitro activities of teicoplanin, daptomycin, ramoplanin, and PD127,391, a new quinolone, were compared with that of vancomycin. Teicoplanin showed the lowest MICs against Enterococcus faecalis. Ramoplanin was slightly more active than the other peptide antibiotics against oxacillin-resistant Staphylococcus aureus. The MICs of the four peptide antibiotics were similar for the oxacillin-susceptible S. aureus. Daptomycin had good activity against staphylococci but was the least active agent against E. faecalis. The MICs of vancomycin against all isolates were in general higher than those of the new antibiotics, with the exceptions of the MICs of daptomycin against E. faecalis and teicoplanin against oxacillin-resistant Staphylococcus epidermidis. PD127,391 was the most active agent against all staphylococcal isolates.     

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.     

In vitro activities of voriconazole, posaconazole, and fluconazole against 4,169 clinical isolates of Candida spp. and Cryptococcus neoformans collected during 2001 and 2002 in the ARTEMIS global antifungal surveillance program

We examined the in vitro activities of voriconazole, posaconazole, and fluconazole against 3,932 isolates of Candida spp. and 237 isolates of Cryptococcus neoformans obtained from over 100 medical centers worldwide during 2001 and 2002. The MICs of the antifungal drugs were determined by broth microdilution tests performed according to the National Committee for Clinical Laboratory Standards (NCCLS) methods using RPMI 1640 as the test medium. Voriconazole and posaconazole were very active against Candida spp. (97-98% susceptible at MICs < or =1 microg/ml) and C. neoformans (98-100% susceptible at MICs < or =1 microg/mL). C. albicans (MIC90, 0.015-0.03 microg/ml) was the most susceptible species of Candida to both agents and C. glabrata (MIC90, 1-2 microg/mL) was the least susceptible. Both voriconazole and posaconazole were more active than fluconazole against all Candida spp. and C. neoformans. These results provide further evidence for the increased spectrum and potency of the new triazoles against a large and geographically diverse collection of opportunistic fungal pathogens.