EV0440 IN-VITRO ACTIVITY OF NEMONOXACIN AGAINST STREPTOCOCCUS PNEUMONIAE AND HAEMOPHILUS INFLUENZAE

Kozlov R.S.1*, Dekhnich A.V.1, Sukhorukova M.V.1, Edelstein M.V.1, Chernavin A.V.2, Samsonov M.Y. 2

1 Institute of Antimicrobial Chemotherapy, Smolensk, RU; 2 “R-Pharm”, Moscow, RU * E-mail: Roman.Kozlov@antibiotic.ru

27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), 22 - 25 April 2017, Vienna, Austria

Table 1. Results of susceptibility testing of S.pneumoniae (n=200) Table 2. MIC distributions for S.pneumoniae (n=200) Background S(%) I(%) R(%) % of strains tested with MIC, mg/l Antimicrobial MIC MIC Antimicrobial 50 90 EUCAST CLSI EUCAST CLSI EUCAST CLSI 0.004 0.008 0.015 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 64 128 256 Amoxicillin 0.03 2 NA 95.5 NA 1.5 NA 3.0 Amoxicillin 61.0 4.5 4.0 4.5 3.0 12.5 6.0 1.5 3.0 Nemonoxacin is a new non-fluorinated quinolone Azithromycin 27.0 34.0 0.5 2.0 0.5 3.5 3.5 2.0 0.5 0.5 1.0 25.0 Azithromycin 0.06 128 63.5 64.0 0.5 3.5 36.0 32.5 Cefixime 7.5 38.5 16.0 7.5 3.5 4.0 4.5 6.0 3.0 3.5 3.0 2.0 1.0 antimicrobial agent in the late stage of clinical NA NA NA NA NA NA Cefixime 0.25 16 Ceftaroline 8.0 49.0 8.5 5.5 5.5 12.0 9.5 1.5 0.5 development. The aim of the study was to evaluate Ceftaroline 0.01 0.25 98.0 99.5 0 NA 2.0 NA Ceftriaxone 6.5 30.0 23.0 6.5 5.5 3.5 2.5 11.0 3.5 3.5 3.5 1.0 the in vitro activity of nemonoxacin, against Ceftriaxone (non-meningitis) 0.03 2 77.5 88.5 14.5 3.5 8.0 8.0 Chloramphenicol 0.5 0.5 5.0 51.5 35.0 2.0 1.0 4.0 0.5 Chloramphenicol 1 2 95.5 94.5 0 0 4.5 5.5 Ciprofloxacin 0.5 3.0 6.5 30.5 45.0 11.5 1.5 0.5 0.5 0.5 S.pneumoniae and H.influenzae. Ciprofloxacin 1 2 0.5 NA 96.5 NA 3.0 NA Clarithromycin 61.5 1.0 1.5 1.5 5.5 3.5 1.5 1.5 0.5 0.5 21.5 Clindamycin 60.8 12.6 1.5 0.5 1.5 1.0 1.0 4.0 2.5 14.6 Clarithromycin 0.03 128 65.5 65.5 5.5 5.5 29.0 29.0 Erythromycin 61.0 4.5 1.5 6.0 3.5 2.0 0.5 2.0 0.5 1.0 3.0 14.5 0.03 128 76.9 75.4 0 1.5 23.1 23.1 Clindamycin Levofloxacin 0.5 1.0 2.0 64.0 32.0 0.5 Methods Erythromycin 0.03 128 73.0 73.0 3.5 3.5 23.5 23.5 Linezolid 1.5 2.5 14.0 66.0 16.0 Levofloxacin 0.5 1 100 100.0 0 0 0 0 Moxifloxacin 2.5 12.5 59.0 25.0 1.0 A total of 200 resent clinical strains of Linezolid 0.50 1 100 100.0 0 0 0 0 Nemonoxacin 2.0 13.5 32.0 46.5 6.0 Moxifloxacin 0.06 0.125 100 100 0 0 0 0 Penicillin 58.5 2.5 5.5 4.5 5.0 6.5 11.0 5.5 0.5 0.5 S.pneumoniae and 50 strains of H.influenzae Spiramycin 17.5 25.5 27.5 3.5 3.0 0.5 2.5 3.5 6.0 3.0 0.5 0.5 6.5 Nemonoxacin 0.06 0.06 NA NA NA NA NA NA Tetracycline 50.5 4.0 2.0 2.5 3.0 6.0 13.5 14.5 2.5 1.5 isolated in different regions of Russia from 0.03 2 61.0 93.5 32.5 5.5 6.5 1.0 Penicillin (non-meningitis) Trimethoprim/Sulfa. 4.5 18.0 13.0 9.5 11.5 5.5 15.0 9.5 12.5 1.0 patients with clinical symptoms of respiratory Spiramycin 0.25 32 NA NA NA NA NA NA Vancomycin 1.0 6.5 32.5 55.5 4.5 infections were included in the study. Tetracycline 0.125 16 59.0 59.0 3.0 3.0 38.0 38.0 Trimethoprim/Sulf. 1 16 56.5 45.0 5.5 17.0 38.0 38.0 The isolation of pathogens from clinical material Vancomycin 0.25 0.25 100 100 0 0 0 0 and identification were performed in the local Table 3. Results of susceptibility testing of H. influenzae (n=50) Table 4. MIC distributions for H. influenzae (n=50) centers in accordance with routine local practice. S(%) I(%) R(%) Antimicrobial MIC MIC % of strains tested with MIC, mg/l After the identification isolates were transported in 50 90 EUCAST CLSI EUCAST CLSI EUCAST CLSI Antimicrobial 0.008 0.015 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 64 128 Amoxicillin/Clavulanic acid 0.03 0.25 100 100 0 0 0 0 the central laboratory (Institute of Antimicrobial Amoxicillin/Clavulanic acid 82 2 16 0 0 Chemotherapy, Smolensk, Russia). Ampicillin 0.13 0.5 94 94 6 6 Ampicillin 2 56 24 12 2 2 2 Azithromycin 1 2 0 100 100 0 0 0 Azithromycin 4 56 36 4 Majority of S.pneumoniae strains were revealed Cefixime 0.03 0.03 100 100 0 0 0 0 Cefixime 2 32 56 4 6 Cefotaxime 0.02 0.03 94 100 0 0 6 0 Cefotaxime 26 54 14 6 from patients with lower (61.5%) and upper Ceftaroline 54 28 12 6 Ceftaroline 0.01 0.03 94 100 0 0 6 0 Ceftibuten 10 16 44 20 2 2 4 2 (34.5%) respiratory tract infections, 6 (3%) 0 0 0 Ceftibuten 0.06 0.13 98 98 2 Chloramphenicol 86 14 isolates were from blood and 2 (1%) – from CSF. Chloramphenicol 0.5 1 100 100 0 0 0 Ciprofloxacin 94 6 Infection location for H.influenzae were: lower Ciprofloxacin 0.02 0.02 100 100 0 0 0 Clarithromycin 2 48 46 4 Clarithromycin 4 8 0 96 100 4 0 0 Ertapenem 18 32 34 4 8 2 2 Levofloxacin 4 64 32 respiratory tract - 58%, upper respiratory tract - Ertapenem 0.02 0.13 96 96 0 0 4 0 Moxifloxacin 60 30 2 8 0.03 0.06 100 100 0 0 0 0 32%, CSF – 8%, blood – 2%. Levofloxacin Nemonoxacin 62 36 2 0 0 0 0 Minimal inhibitory concentrations (MIC) for the Moxifloxacin 0.02 0.03 100 100 Tetracycline 20 80 Nemonoxacin 0.01 0.02 NA NA NA NA NA NA Trimethoprim/Sulfa. 4 4 10 30 10 2 6 12 6 16 nemonoxacin and other antimicrobials were Tetracycline 0.5 0.5 100 100 0 0 0 0 determined using broth microdilition method Trimethoprim/Sulfa. 0.5 16 58 58 2 8 40 34 according to EUCAST methodology. Conclusions

 Nemonoxacin has shown high in vitro activity against all tested S.pneumoniae strains with the MIC90 values being 1, 4 and 5 dilutions lower than those for moxifloxacin, Results levofloxacin and ciprofloxacin, respectively. Activity of nemonoxacin against S.pneumoniae isolates was not altered by the presence of resistance to other classes of antimicrobials. Results of susceptibility testing and MIC  All quinolones tested, including nemonoxacin, demonstrated excellent activity against H.influenzae isolates. distributions for S.pneumoniae and H.influenzae  Overall, according to MIC50/90 values and MIC ranges nemonoxacin was one of the most in vitro active agents among all antimicrobials tested and could be considered are presented in Table 1-2 and 3-4, respectively. as a promising option for the treatment of infections caused by S.pneumoniae and H.influenzae.