Activities of ABT-773 against Listeria monocytogenes and coryneform bacteria of clinical interest

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Ap . 2003, p. 1403–1406 Vol. 47, No. 4 0066-4804/03/$08.00⫹0 DOI: 10.1128/AAC.47.4.1403–1406.2003 Copy igh © 2003, Ame ican Socie y o Mic obiology. All Righ s Rese ed. Ac i i ies o ABT-773 agains Lis e ia monocy ogenes and Co yne o m Bac e ia o Clinical In e es Ma ía del Ca men Conejo, 1 Luis Ma ínez-Ma ínez, 1,2 *A ´l a o Pascual, 1,2 Ana Isabel Sua´ ez, 2 and E elio J. Pe ea 1,2 Depa men o Mic obiology, School o Medicine, 1 and Uni e si y Hospi al Vi gen Maca ena, 2 Uni e si y o Se ille, Se ille, Spain Recei ed 29 July 2002/Re u ned o modi ica ion 9 Oc obe 2002/Accep ed 31 Decembe 2002 The in i o ac i i ies o ABT-773 we e e alua ed agains 15 Lis e ia monocy ogenes s ains and 196 co yne- o m bac e ia isola ed om clinical samples. One hund ed pe cen o he L.monocy ogenes s ains we e inhibi ed by <0.015 ␮g o ABT-773/ml. MICs o ABT-773 (␮g/ml) a which 50% o he isola es es ed we e inhibi ed (MIC 50 s) and MIC 90 s o o he o ganisms we e 0.125 and 0.5 (Co ynebac e ium amycola um), 1 and >32 (Co ynebac e ium jeikeium), 0.03 and >32 (Co ynebac e ium minu issimum), >32 and >32 (Co ynebac e ium pseudodiph he i icum and Co ynebac e ium u ealy icum), 0.125 and >32 (Co ynebac e ium s ia um), and 0.03 and 0.5 (Rhodococcus equi), espec i ely. Two ele an aspec s ela ed o co yne o m bac e ia ha e become signi ican du ing he las decade: he ecogni ion o he medical impo ance o some species, including Co ynebac- e ium jeikeium,Co ynebac e ium u ealy icum,Co ynebac e ium s ia um,Co ynebac e ium amycola um, and Co ynebac e ium minu issimum, and he changes in he axonomy o hese o - ganisms leading o he ecogni ion o a la ge numbe o new species and he ede ini ion o al eady known o ganisms (1, 2, 4, 6, 8). I is c i ical ha s udies o he ac i i ies o an imic o- bial agen s be based on es ing mic oo ganisms iden i ied ac- co ding o he new axonomic c i e ia, in o de o eally ob ain clinically signi ican in o ma ion and o allow he compa ison o da a ob ained om di e en labo a o ies (3, 5, 13, 19, 24). Un o una ely, he e is ye no s anda dized me hodology o suscep ibili y es ing o co yne o m bac e ia. The NCCLS has no de ined b eakpoin s o clinical ca ego ies o an imic obial agen s agains co yne o m bac e ia, and in he case o Lis e ia spp. only he ca ego y o suscep ibili y o ampicillin and peni- cillin has been sugges ed (16). The e is scan in o ma ion on he ac i i ies o an imic obial agen s agains co yne o m bac- e ia (4–6, 9). C.jeikeium,C.u ealy icum, and C.amycola um a e usually mul i esis an o ganisms, and only glycopep ides emain uni e sally ac i e agains hese species (4–6, 18, 19, 22, 23). Some epo s sugges ha o he species may be suscep ible o commonly used an imic obial agen s, bu we lack eliable clinical e idence suppo ing hese in i o obse a ions. I is necessa y o e alua e he ac i i ies o new an imic obial agen s agains co yne o m bac e ia o clinical impo ance (3, 7, 10–12, 19). I has been shown p e iously ha ke olides show a b oade spec um o ac i i y han do e e ence mac olides, being ac i e agains mac olide-suscep ible g am-posi i e cocci and agains g am-posi i e o ganisms in which mac olide esis ance is caused by ac i e e lux o inducible p oduc ion o me hylase (21). In a p e ious s udy we showed ha he new ke olide eli h omycin was mo e ac i e han we e 14- and 16-membe ed mac olides, azi h omycin, o clindamycin agains many co yne- o m bac e ia and had high in i o ac i i y agains Lis e ia monocy ogenes (10). The objec i e o his s udy was o e alua e he in i o ac i i ies o ABT-773 in compa ison wi h o he compounds agains L.monocy ogenes and di e en species o co yne o m bac e ia isola ed om clinical samples. Two hund ed ele en o ganisms isola ed om clinical sam- ples a he Depa men o Clinical Mic obiology, Uni e si y Hospi al Vi gen Maca ena, Se ille, Spain, we e e alua ed, in- cluding he ollowing species (numbe o s ains): L.monocy- ogenes (15), C.amycola um (40), C.jeikeium (40), C.minu is- simum (14), Co ynebac e ium pseudodiph he i icum (12), C. s ia um (40), C.u ealy icum (40), and Rhodococcus equi (10). Mic oo ganisms we e iden i ied acco ding o he me hod o Funke e al. (4), by using API-CORYNE s ips and addi ional pheno ypic es s when necessa y. A e iden i ica ion, o gan- isms we e main ained in yp ic soy b o h–10% glyce ol a ⫺80°C. The ollowing e e ence s ains we e also es ed: C. jeikeium ATCC 43734, C.s ia um ATCC 6940, and C.u ea- ly icum ATCC 43042. S aphylococcus au eus ATCC 29213 and En e ococcus aecalis ATCC 29212 we e used as con ol s ains o suscep ibili y es ing assays. The ollowing compounds we e s udied: ABT-773 (Abbo ), ce u oxime (Sigma), clinda- mycin (Sigma), co- imoxazole (Gayoso, Mad id, Spain), e y h omycin (Sigma), and ancomycin (Sigma). Solu ions o an imic obial agen s we e p epa ed on he same day as es ing, acco ding o he manu ac u e ’s ins uc ions. The MICs o he abo e-indica ed an imic obial agen s we e de e mined, as p e- iously desc ibed, by in-house mic odilu ion acco ding o NC- CLS guidelines (15, 16), wi h he excep ion ha , when C. jeikeium and C.u ealy icum (lipophilic o ganisms) we e es ed, he b o h was supplemen ed wi h 0.5% Tween 80 (Di co, De- oi , Mich.). Pla es we e inocula ed wi h a suspension (ap- p oxima ely 5 ⫻10 5 CFU/ml) in Muelle -Hin on b o h (plus 0.5% Tween 80 in he case o C.jeikeium and C.u ealy icum) p epa ed om bac e ia g own on Columbia aga wi h 5% sheep blood o 24 o 48 h. Pla es we e incuba ed, a e inoc- * Co esponding au ho . Mailing add ess: Depa men o Mic obi- ology, School o Medicine, Uni e si y o Se ille, Apdo. 914, 41080 Se ille, Spain. Phone: 34 95 500 8287. Fax: 34 95 437 7413. E-mail: [email p o ec ed]. 1403 on July 31, 2017 by USE/BCTA.GEN UNIVERSITARIAh p://aac.asm.o g/Downloaded om ula ion, a 35°C o 20 o 24 h, o (in he case o C.jeikeium and C.u ealy icum) o up o 48 h, o allow bac e ial g ow h in con ol (an ibio ic- ee) wells o he mic o i e pla e. The ac i i ies o he agen s he ein es ed ha e been consid- e ed in e ms o MIC 50 s (MICs a which 50% o he isola es es ed a e inhibi ed), MIC 90 s, and MIC anges (Table 1). Ad- di ionally, he numbe s and pe cen ages o s ains inhibi ed a each concen a ion o ABT-773 and he ela ed d ugs e y h- omycin and clindamycin ha e also been de e mined (Table 2). All s ains o L.monocy ogenes we e inhibi ed by ⱕ0.015 ␮go ABT-773/ml. MIC 90 s o ABT-773 we e ⱖ32- and ⱖ128- old lowe han hose o e y h omycin and clindamycin, espec- i ely. In e es ingly, his alue is also much lowe han ha ecen ly ob ained in ou labo a o y o eli h omycin, o which he MIC 50 and MIC 90 we e 0.125 and 0.25 ␮g/ml, espec i ely. Ou esul s a e simila o hose ob ained in a p e ious s udy (17), in which all 24 s ains o L.monocy ogenes we e inhibi ed a 0.03 ␮g/ml. This good in i o ac i i y o ABT-773 agains L. monocy ogenes con as s wi h i s ela i ely high e ec i e dose (100.1 mg/kg o body weigh /day) in an animal model o sepsis caused by L.monocy ogenes (14). Vancomycin and co- imox- azole also showed good in i o ac i i ies agains L.monocy- ogenes. ABT-773 inhibi ed highe pe cen ages o s ains o all Co ynebac e ium species and o R.equi e alua ed han did e y h omycin. A a concen a ion o 0.5 ␮g/ml ( he b eakpoin o suscep ibili y o e y h omycin agains S aphylococcus spp.) he pe cen ages o inhibi ion by ABT-773 and e y h omycin we e 92.5 and 15.0% o C.amycola um, 90.0 and 60.0% o R. equi, 62.5 and 20.0% o C.s ia um, 50.0 and 37.5% o C. minu issimum, 47.5 and 2.5% o C.jeikeium, 33.3 and 25.0% o C.pseudodiph he i icum, and 7.5 and 5.0% o C.u ealy i- cum, espec i ely. Clindamycin was e en less ac i e han e y h- omycin agains he es ed s ains. We ha e p e iously e alu- a ed he ac i i ies o eli h omycin agains co yne o m bac e ia, wi h he same me hodology used in his s udy (10). ABT-773 showed an ac i i y simila o ha o eli h omycin agains co yne o m bac e ia, excep in he case o C.s ia um, o which he MIC 50 and MIC 90 o eli h omycin (0.03 and 0.06 ␮g/ml, espec i ely) we e lowe han hose o ABT-773 (0.125 and ⬎32 ␮g/ml, espec i ely). The ac ual easons o he di - e ence in he ac i i ies o he wo ke olides agains C.s ia um a e p esen ly unknown. I could well be ha ABT-773 is in- insically less ac i e han eli h omycin is agains his o gan- ism, bu since he isola es e alua ed in his s udy we e mo e ecen han hose in he s udy wi h eli h omycin, he obse ed lowe suscep ibili y o C.s ia um o ABT-773 could be due o a ecen inc ease in he le el o esis ance o C.s ia um o ke olides, a si ua ion al eady desc ibed o luo oquinolones (11). The di e ences in suscep ibili ies o ABT-773 and o e y h- omycin in he es ed s ains indica e ha mac olide- esis an co yne o m bac e ia a e s ill inhibi ed by ke olides. The mech- anisms unde lying his obse a ion emain unde ined, since he mechanisms o esis ance o bo h mac olides and ke olides in co yne o m bac e ia a e poo ly known. The e mC gene has been epo ed o be p esen in mos C.s ia um s ains esis- an o e y h omycin (20). The exis ence o bimodal popula- ions among C.minu issimum,C.pseudodiph he i icum,C.s i- a um, and C.u ealy icum sugges s ha hese species may TABLE 1. Ranges, MIC 50 s, and MIC 90 s o an imic obial agen s o L. monocy ogenes and co yne o m bac e ia Bac e ium (no. o isola es) and an imic obial agen MIC (␮g/ml) Range MIC 50 MIC 90 Lis e ia monocy ogenes (15) a ABT-773 ⱕ0.015 ⱕ0.015 ⱕ0.015 E y h omycin 0.125–0.5 0.25 0.5 Clindamycin 0.5–222 Co- imoxazole 0.015–0.03 0.015 0.03 Vancomycin 0.5–111 C. amycola um (40) ABT-773 ⱕ0.015–2 0.125 0.5 E y h omycin ⱕ0.06–⬎128 16 128 Clindamycin 0.25–⬎64 ⬎64 ⬎64 Ce u oxime ⱕ0.03–⬎128 0.25 0.5 Co- imoxazole 0.25–⬎16 ⬎16 ⬎16 Vancomycin 0.25–1 0.5 0.5 C. jeikeium (40) ABT-773 ⱕ0.015–⬎32 1 ⬎32 E y h omycin ⱕ0.06–⬎128 ⬎128 ⬎128 Clindamycin 0.25–⬎64 ⬎64 ⬎64 Ce u oxime 0.06–⬎64 ⬎64 ⬎64 Co- imoxazole 0.125–⬎16 ⬎16 ⬎16 Vancomycin 0.5–1 0.5 1 C. minu issimum (14) ABT-773 ⱕ0.015–⬎32 0.03 ⬎32 E y h omycin ⱕ0.06–⬎128 32 ⬎128 Clindamycin 0.06–⬎64 ⬎64 ⬎64 Ce u oxime 0.06–⬎64 0.5 32 Co- imoxazole 0.06–⬎16 2 ⬎16 Vancomycin 0.125–1 0.25 0.5 C. pseudodiph he i icum (12) ABT-773 ⱕ0.015–⬎32 ⬎32 ⬎32 E y h omycin ⱕ0.06–⬎128 ⬎128 ⬎128 Clindamycin ⱕ0.03–⬎64 ⬎64 ⬎64 Ce u oxime ⱕ0.03–1 0.125 0.5 Co- imoxazole 0.5–⬎16 4 ⬎16 Vancomycin 0.25–0.5 0.25 0.25 C. s ia um (40) ABT-773 ⱕ0.015–⬎32 0.125 ⬎32 E y h omycin ⱕ0.06–⬎128 8 ⬎128 Clindamycin 1–⬎64 ⬎64 ⬎64 Ce u oxime 0.5–⬎64 2 4 Co- imoxazole 0.5–16 4 8 Vancomycin 0.125–0.5 0.25 0.25 C. u ealy icum (40) ABT-773 ⱕ0.015–⬎32 ⬎32 ⬎32 E y h omycin ⱕ0.06–⬎128 ⬎128 ⬎128 Clindamycin 0.125–⬎64 ⬎64 ⬎64 Ce u oxime ⬎64 ⬎64 ⬎64 Co- imoxazole ⬎16 ⬎16 ⬎16 Vancomycin 0.125–1 0.5 0.5 Rhodococcus equi (10) ABT-773 ⱕ0.015–4 0.03 0.5 E y h omycin ⱕ0.06–⬎128 0.5 ⬎128 Clindamycin 0.125–⬎64 4 ⬎64 Ce u oxime 0.5–⬎64 8 ⬎64 Co- imoxazole 0.25–⬎16 16 ⬎16 Vancomycin 0.5 0.5 0.5 a Following he NCCLS sugges ion (16), MICs o ce u oxime agains L. mono- cy ogenes a e no de ailed. 1404 NOTES ANTIMICROB.AGENTS CHEMOTHER. on July 31, 2017 by USE/BCTA.GEN UNIVERSITARIAh p://aac.asm.o g/Downloaded om exp ess a simila de e minan o esis ance, bu u he s udies a e ob iously needed in his a ea. All co yne o m bac e ia e alua ed we e inhibi ed by 1 ␮go ancomycin/ml, in ag eemen wi h p e ious s udies (10, 19, 23). On he o he hand, co- imoxazole was poo ly ac i e agains co yne o m bac e ia, and o his agen all MIC 50 s agains C. amycola um,C.jeikeium, and C.u ealy icum we e ⬎16 ␮g/ml. MIC 50 s o co- imoxazole we e highe han 2/38 ␮g/ml ( he b eakpoin o s aphylococci ha may be conside ed as a e - e ence indica o ) o C.pseudodiph he i icum,C.s ia um, and R.equi. Ce u oxime was also poo ly ac i e in i o agains mos co yne o m bac e ia. Ce u oxime showed good in i o ac i i- ies agains C.amycola um (MIC 90 , 0.5 ␮g/ml), C.pseudodiph- he i icum (MIC 90 , 0.5 ␮g/ml), and o a lesse ex en C.s ia um (MIC 90 ,4␮g/ml). Al hough he same pe cen ages o C.amy- cola um and C.s ia um s ains we e inhibi ed by 8 ␮go ce u oxime/ml (100%), his compound was mo e ac i e agains he o me species, because he pe cen ages o inhibi ion a 0.5 ␮g/ml we e 92.5% o C.amycola um and 5% o C.s ia um. In conclusion, ABT-773 shows e y good in i o ac i i y agains L.monocy ogenes and also inhibi s a signi ican numbe o co yne o m bac e ia o clinical ele ance. ABT-773 shows good in i o ac i i ies agains C.amycola um and R.equi and mode a e ac i i ies agains C.minu issimum and C.s ia um and he mul i esis an species C.jeikeium. ABT-773 is poo ly ac i e agains C.pseudodiph he i icum and C.u ealy icum. This s udy was suppo ed by a g an om Abbo Labo a o ies. REFERENCES 1. Collins, M. D., R. A. Bu on, and D. Jones. 1988. Co ynebac e ium amyco- la um sp. no ., a new mycolic acid-less Co ynebac e ium species om human skin. FEMS Mic obiol. Le . 49:349–352. 2. Funke, G., P. A. Lawson, K. A. Be na d, and M. D. Collins. 1996. Mos Co ynebac e ium xe osis s ains iden i ied in he ou ine clinical labo a o y co espond o Co ynebac e ium amycola um. J. Clin. Mic obiol. 34:1124– 1128. 3. Funke, G., V. Pu¨n e , and A. on G ae eni z. 1996. An imic obial suscep i- bili y pa e ns o some ecen ly es ablished co yne o m bac e ia. An imic ob. Agen s Chemo he . 40:2874–2878. 4. Funke, G., A. on G ae eni z, J. E. Cla idge, and K. A. Be na d. 1997. Clinical signi icance o co yne o m bac e ia. Clin. Mic obiol. Re . 10:125– 159. 5. Ga cía-Rod íguez, J. A., J. E. Ga cía Sa´nchez, J. L. Mun˜oz Bellido, T. Neb eda Mayo al, E. Ga cía Sa´nchez, and I. Ga cía Ga cía. 1991. In i o ac i i y o 79 an imic obial agen s agains Co ynebac e ium g oup D2. An i- mic ob. Agen s Chemo he . 35:2140–2143. 6. Ma ínez-Ma ínez, L. 1998. Clinical signi icance o newly ecognized co yne o m bac e ia. Re . Med. Mic obiol. 9:55–68. 7. Ma ínez-Ma ínez, L., P. Joyanes, A. I. Sua´ ez, and E. J. Pe ea. 2001. Ac i i ies o gemi loxacin and i e o he an imic obial agen s agains Lis e ia monocy ogenes and co yne o m bac e ia isola ed om clinical samples. An- imic ob. Agen s Chemo he . 45:2390–2392. 8. Ma ínez-Ma ínez, L., A. Pascual, K. Be na d, and A. I. Sua´ ez. 1996. An imic obial suscep ibili y pa e n o Co ynebac e ium s ia um. An imi- c ob. Agen s Chemo he . 40:2671–2672. 9. Ma ínez-Ma ínez, L., M. C. O ega, and A. I. Sua´ ez. 1995. Compa ison o E- es wi h b o h mic odilu ion and disk di usion o suscep ibili y es ing o co yne o m bac e ia. J. Clin. Mic obiol. 33:1318–1321. 10. Ma ínez-Ma ínez, L., A. Pascual, A. I. Sua´ ez, and E. J. Pe ea. 1998. In i o ac i i ies o ke olide HMR 3647, mac olides, and clindamycin agains co yne o m bac e ia. An imic ob. Agen s Chemo he . 42:3290–3292. TABLE 2. Pe cen ages o s ains o L. monocy ogenes and co yne o m bac e ia inhibi ed a he indica ed concen a ions o ABT-773, e y h omycin, and clindamycin Bac e ium (no. o isola es) An imic obial agen % o s ains inhibi ed a concn (␮g/ml): ⱕ0.015 0.03 0.06 0.125 0.25 0.5 1248163264⬎64 C. amycola um (40) ABT-773 30.0 35.0 45.0 75.0 85.0 92.5 95.0 100 E y h omycin 15.0 30.0 35.5 55.0 80.0 87.5 100 Clindamycin 10 15.0 17.5 100 C. jeikeium (40) ABT-773 7.5 12.5 30 42.5 45.0 47.5 60.0 62.5 65.0 100 E y h omycin 2.5 5.0 7.5 15.0 20.0 100 Clindamycin 2.5 100 C. minu issimum (14) ABT-773 42.9 57.2 64.3 100 E y h omycin 28.6 35.7 42.9 50.0 57.2 100 Clindamycin 7.2 14.3 28.6 42.9 100 C. pseudodiph he i icum (12) ABT-773 33.3 41.7 100 E y h omycin 16.7 25.0 100 Clindamycin 8.3 25.0 100 C. s ia um (40) ABT-773 27.5 30 47.5 57.5 60.0 62.5 100 E y h omycin 20 25.0 47.5 55.0 60.0 62.5 100 Clindamycin 2.5 12.5 20.0 100 C. u ealy icum (40) ABT-773 5.0 7.5 10.0 100 E y h omycin 50 100 Clindamycin 5.0 100 L. monocy ogenes (15) ABT-773 100 E y h omycin 6.7 73.3 100 Clindamycin 6.7 40.0 100 R. equi (10) ABT-773 40.0 60.0 70.0 80.0 90.0 100 E y h omycin 20.0 30.0 60.0 70.0 100 Clindamycin 20.0 30.0 40.0 70.0 100 VOL. 47, 2003 NOTES 1405 on July 31, 2017 by USE/BCTA.GEN UNIVERSITARIAh p://aac.asm.o g/Downloaded om 11. Ma ínez-Ma ínez, L., A. Pascual, A. I. Sua´ ez, and E. J. Pe ea. 1999. In i o ac i i y o le o loxacin, o loxacin and D-o loxacin agains co yne o m bac e ia o clinical in e es . J. An imic ob. Chemo he . 43(Suppl. C):27–32. 12. Ma ínez-Ma ínez, L., A. I. Sua´ ez, M. C. O ega, and E. J. Pe ea. 1994. Compa a i e in i o ac i i ies o new quinolones agains co yne o m bac e- ia. An imic ob. Agen s Chemo he . 38:1439–1441. 13. Ma ínez-Ma ínez, L., A. I. Sua´ ez, J. Wins anley, M. C. O ega, and K. Be na d. 1995. Pheno ypic cha ac e is ics o 31 s ains o Co ynebac e ium s ia um isola ed om clinical samples. J. Clin. Mic obiol. 33:2458–2461. 14. Mi en, M. J., J. Meulb oek, M. Nukkala, L. Paige, K. Ja is, A. Oleksijew, A. To cimak, L. He nandez, J. D. Alde , P. Ewing, Y. S. O , Z. Ma, A. M. Nilius, K. Mollison, and R. K. Flamm. 2001. E icacies o ABT-773, a new ke olide, agains expe imen al bac e ial in ec ions. An imic ob. Agen s Che- mo he . 45:2585–2593. 15. Na ional Commi ee o Clinical Labo a o y S anda ds. 1997. Me hods o dilu ion an imic obial suscep ibili y es s o bac e ia ha g ow ae obically, 4 h ed. App o ed s anda d. NCCLS documen M/-A4. Na ional Commi ee o Clinical Labo a o y S anda ds, Wayne, Pa. 16. Na ional Commi ee o Clinical Labo a o y S anda ds. 2002. Pe o mance s anda ds o an imic obial suscep ibili y es ing, 12 h in o ma ional supple- men . Na ional Commi ee o Clinical Labo a o y S anda ds, Wayne, Pa. 17. Nilius, A. M., M. H. Bui, L. Alme , D. Hensey-Rudlo , J. Beye , Z. Ma, Y. S. O , and R. K. Flamm. 2001. Compa a i e in i o ac i i y o ABT-773, a no el an ibac e ial ke olide. An imic ob. Agen s Chemo he . 45:2163–2168. 18. Philippon, P., and E. Bime . 1990. In i o suscep ibili y o Co ynebac e ium g oup D2 and Co ynebac e ium jeikeium o wel e an ibio ics. Eu . J. Clin. Mic obiol. In ec . Dis. 9:892–895. 19. Riegel, P., R. Ruimy, R. Ch is en, and H. Mon eil. 1996. Species iden i ies and an imic obial suscep ibili ies o co ynebac e ia isola ed om a ious clinical sou ces. Eu . J. Clin. Mic obiol. In ec . Dis. 15:657–662. 20. Robe s, M. C., R. B. Leona d, R. B. B iselden, F. D. Schoenknech , and M. B. Coyle. 1992. Cha ac e iza ion o an ibio ic esis an Co ynebac e ium s ia um s ains. J. An imic ob. Chemo he . 30:463–474. 21. Sho idge, V. D., P. Zhong, Z. Cao, J. M. Beye , L. S. Alme , N. C. Rame , S. Z. Dok o , and R. K. Flamm. 2002. Compa ison o in i o ac i i ies o ABT-773 and eli h omycin agains mac olide-suscep ible and - esis an s ep ococci and s aphylococci. An imic ob. Agen s Chemo he . 46:783–786. 22. So iano, F., C. Pon e, A. To es, and R. Fe na´ndez-Roblas. 1987. Suscep i- bili y o u ina y isola es o Co ynebac e ium g oup D2 o i een an imic o- bials and ace ohyd oxamic acid. J. An imic ob. Chemo he . 20:349–355. 23. So iano, F., R. Fe na´ndez-Roblas, J. Zapa diel, J. L. Rod íguez-Tudela, P. A ile´s, and M. Rome o. 1989. Inc easing incidence o Co ynebac e ium g oup D2 s ains esis an o no loxacin and cip o loxacin. Eu . J. Clin. Mic obiol. In ec . Dis. 8:117–118. 24. So iano, F., J. Zapa diel, and N. Nie o. 1995. An imic obial suscep ibili ies o Co ynebac e ium species and o he non-spo e- o ming g am-posi i e ba- cilli o 18 an imic obial agen s. An imic ob. Agen s Chemo he . 39:208–214. 1406 NOTES ANTIMICROB.AGENTS CHEMOTHER. on July 31, 2017 by USE/BCTA.GEN UNIVERSITARIAh p://aac.asm.o g/Downloaded om