CP-99,219 is a trifluoronaphthyridone with significant antibacterial activity that includes the family Enterobacteraceae (MICs for 90% of the strains tested [MIC90s], <0.015 to 0.5 ,ug/ml), MoraxeUla catarrhalis, Haemophilus influenzae, and gonococci (MICs, <0.015 p.g/ml). LegioneUla spp. were also CP-99,219 susceptible, with MICs of 0.008 to 0.12 ,ug/ml. 219 demonstrated activity greater than that of ciprofloxacin, ofloxacin, or enoxacin against Pseudomonas aeruginosa (MICg., 1 p,g/ml), Xanthomonas maltophilia (MIC90, 2 ,ug/ml), Staphylococcus haemolyticus (MIC90, 0.5 ,ug/ml), Enterococcus faecalis (MIC90, 1 ,ug/ml), and pneumococci (MIC90, 0.12 ,ug/ml). Numerous ciprofloxacin-resistant isolates were susceptible to 219, a new compound showing potential value for further in vivo trials.CP-99,219 is a novel investigational fluoroquinolone with a structure differing from those of norfloxacin, ciprofloxacin, and enoxacin (1,2,4,8). It contains the C-7 ring moiety 7-(3-azabicyclo[3.1.0]hexyl) on a basic naphthyridone configuration. The bicyclo C-7 substitution has been previously evaluated and described in CP-74,667 (5). The 1-N substitution of CP-99,219 is a difluorinated structure identical to that of tosufloxacin (3, 10) that produces enhanced activity against some ciprofloxacin-resistant organisms. In this study, we compared CP-99,219 activity with those of four clinically available quinolones (ciprofloxacin, enoxacin, norfloxacin, and ofloxacin) by using standardized methods.Isolates

RP59500, a semisynthetic pristinamycin combination, and 14 other antimicrobial agents were tested against 108 Legionella strains. Of the ten macrolide, lincosamine and streptogramin agents tested, the new streptogramin RP59500 ranked seventh in order of activity against Legionella pneumophila on the basis of MIC90 results as follows: clarithromycin = 14-OH clarithromycin (MIC90 0.12 mg/l) > roxithromycin > erythromycin = tylosin = virginiamycin > RP59500 (MIC90 1 mg/l) = azithromycin > dirithromycin > clindamycin (MIC90 8 mg/l). Of all 14 drugs tested in this study, rifampicin was the most potent with an MIC90 of 0.008 mg/l. In this retrospective study of Legionella strains (1981-1990 isolates), we observed no trend toward resistance to the agents investigated.

The antimicrobial activities of two investigational fluoroquinolones (CI-960 and E4695) were compared with those of five similar compounds and four comparison drugs against 103 strains of LegioneUa pneumophila and five other LegioneUla species type strains. When concentrations inhibiting 90%o of strains tested (MIC90s) for L. pneumophila were determined, CI-960 and temafloxacin emerged as the most active (0.015 pg/ml) and were followed in potency by E4695 (0.03 pg/mi). This activity was two-to fourfold greater than that of the reference drug, ciprofloxacin, and approached that of rifampin (MIC90, 0.008 pg/ml). All fluoroquinolones studied were more active than erythromycin (MIC90, 0.5 ,jLg/ml). These two investigational fluoroquinolones appear well suited for further in vivo study of legionellosis therapy.For more than 15 years, Legionella pneumophila has been recognized as a significant cause of lower respiratory infections (4). Because Legionella species are able to live and replicate intracellularly, therapeutic antimicrobial agents that penetrate bacterial cell walls and high intracellular concentrations are required (6). Of the comparison compounds tested in this and other studies, rifampin and erythromycin have been the drugs of choice, maintaining good in vitro and in vivo activities against Legionella species (1,4,5,7,8,10,14).In this study, the testing procedures used the buffered starch-yeast extract agar and broth medium described by Sawatari et al. (14). This medium contains no charcoal, which has been observed to inactivate some anti-Legionella drugs (1,10 The fluoroquinolones and four comparison antimicrobial agents were tested in charcoal-free buffered starch-yeast extract agar (Table 1). The seven fluoroquinolones were generally quite potent (MICs, <0.12 ,ug/ml) against the L. pneumophila strains. The activity rank order of the fluoroquinolones was as follows: CI-960 (MIC for 90% of strains tested [MIC0], 0.015 p,g/ml) = temafloxacin > E4695 > ciprofloxacin = fleroxacin = ofloxacin > lomefloxacin (MIC90, 0.06 ,ug/ml). Among the three investigational compounds, CI-960 was the most potent, having all MICs between 0.004 and 0.015 ,ug/ml. The fluoroquinolones were generally more potent than the other comparison compounds, tetracycline (MIC90, 8 p,g/ml) and imipenem (MICg,1 ,ug/ml). The macrolide comparison agent, erythromycin, also exhibited activity against these isolates (MIC90, 0.5 ,ug/ml). Rifampin MICs ranged from .0.002 to 0.03 ,ug/ml, i.e., it was the most potent drug tested. The activity of temafloxacin against L. pneumophila was superior to that of ciprofloxacin, confirming the results of an earlier study (7).These compounds were very active against five representative strains of four other Legionella spp. (Table 2)

Preliminary interpretive zone diameter criteria were calculated for the 5-jig cefdinir disk diffusion test by using two potential MIC breakpoints (.0.5 and s1 ,ug/mi). The absolute agreement between tests ranged from 85.9 to 92.4%, and the false-susceptibility errors were principally contributed by the Enterobacter spp. (2.2% error). One proposed criterion was 220-mm zone diameter (<1 jig/ml) for susceptibility and .16-mm zone diameter (>2 jig/ml) for resistance to cefdinir. Clinical laboratory users of the disk diffusion method should be cautioned about the possibility of very major interpretive errors among enterobacter isolates.