- Email: [email protected]
P827 Infiuence of polysorbate 80 on susceptibility of Gram-positive bacteria to oritavancin
S210
17th ECCMID / 25th ICC, Posters
bactericidal lipoglycopeptide, has recently completed two Phase 3 clinical trials for the treatment of complicated skin and skin structure infections. Ongoing trials are assessing TLV for the treatment of hospitalacquired pneumonia. Because TLV will be used in the hospital setting, profiling its activity against enterococci is important. Methods: A total of 434 Enterococcus faecalis (EF) and 348 E. faecium (EM) isolates were collected from Europe (35 hospital sites in 14 countries) during 2004–2005. Isolates were centrally tested by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) methodology (M7-A7) against TLV and comparators. Results were analysed according to blood and non-blood specimen sources (SPECs). Results: The vancomycin-nonsusceptible (VAN-NS) rate for all EF was 5.5% and the VAN-NS rate for EM was 22.7%. The activity of TLV against the EF and EM isolates is shown in the Table. Conclusion: TLV demonstrated potent activity against all EF and EM isolates, regardless of SPEC. Based on MIC90 values, TLV was 16-fold more potent against vancomycin-susceptible (VAN-S) isolates compared with VAN-NS isolates among EF and EM. This evaluation of TLV activity will provide a baseline for comparison of in vitro activity as clinical development and use continues. Activity of telavancin against Enterococcus faecalis (EF) and E. faecium (EM) isolates Organism
Specimen
Phenotypea
source EF
Blood
Non-blood
EM
Blood
Non-blood
a VAN-S/VAN-NS,
All VAN-S VAN-NS All VAN-S VAN-NS All VAN-S VAN-NS All VAN-S VAN-NS
No. of
MIC (mg/L)
isolates
Range
MIC90
181 164 17 253 246 7 144 100 44 204 169 35
0.06−8 0.06−2 4−8 0.06−8 0.06−8 0.5−8 0.03−8 0.03−2 0.12−8 0.03−8 0.03−2 0.12−8
1 0.5 8 0.5 0.5 8 4 0.25 4 2 0.25 4
vancomycin-susceptible/nonsusceptible.
P827 Influence of polysorbate 80 on susceptibility of Gram-positive bacteria to oritavancin F.F. Arhin, I. Sarmiento, A. Belley, G. McKay, D. Draghi, P. Grover, D. Sahm, T.J. Parr Jr., G. Moeck (Saint Laurent, CA; Herndon, US) Objectives: Oritavancin (ORI) is a lipoglycopeptide (LG) with activity against Gram-positive bacteria. Broth microdilution (BMD) assays with dalbavancin, another LG, require 0.002% polysorbate 80 (P80). Following initial observations that P80 reduced ORI BMD minimum inhibitory concentrations (MICs) for reference strains of Staphylococcus aureus (Sa) ATCC 29213 and Enterococcus faecalis (Ef) ATCC 29212 but not for Streptococcus pneumoniae (Sp) ATCC 49619, we examined the effect of P80 on ORI MICs for 301 clinical isolates of these three genera. Methods: BMD assays were conducted on clinical isolates of Sa (n = 76), coagulase-negative staphylococci (CNS; n = 26), Ef (n = 70), E. faecium (Em; n = 30), Sp (n = 19), S. agalactiae (n = 29), S. pyogenes (n = 29), Groups C and G streptococci (n = 8), and Viridans Group streptococci (n = 14), either following CLSI guidelines (no P80) or with P80, in parallel. When tested in the presence of P80, ORI, vancomycin (VAN) and teicoplanin (TEI) were dissolved in 0.002% P80 and maintained in 0.002% P80 thereafter. Reference strains of Sa, Ef and Sp were tested concurrently.
MIC range (MIC 90a ), mg/L
Enterococci E. faecalis (n = 70) E. faecium (n = 30) Staphylococci S. aureus (n = 76) CNS (n = 26) Streptococci S. agalactiae (n = 29) S. pneumoniae (n = 19) S. pyogenes (n = 29) Group C and G (n = 8) Viridans group (n = 14)
ORI
ORI+P80
TEI
TEI+P80
VAN
VAN+P80
0.12−4 (2)
0.008−0.5 (0.12) 0.004−0.5 (0.25)
0.06−64 (0.5) 0.12–256 (64)
0.06−64 (0.12) 0.06–128 (128)
0.12–>256 (2) 0.25–>256 (>256)
0.5–>256 (2) 0.25–>256 (>256)
0.5−1 (1)
0.5−16 (1)
0.12−4 (2)
0.12−2 (0.5) 0.06−4 (2)
0.5−2 (1)
0.5−2 (2)
0.03–0.12 (0.06) 0.015–0.06 (0.06) 0.001–0.25 (0.06) 0.03–0.06 (na) 0.002–0.12 (0.06)
0.03–0.12 (0.06) 0.015–0.06 (0.06) 0.015–0.06 (0.03) 0.03–0.06 (na) 0.002–0.25 (0.12)
0.25−0.5 (0.5) 0.12−0.5 (0.25) 0.25−0.5 (0.25) 0.25−0.5 (na) 0.25−1 (0.5)
0.25−0.5 (0.5) 0.12−0.5 (0.25) 0.25−0.5 (0.25) 0.25−0.5 (na) 0.25−0.5 (0.5)
0.12−4 (4)
1−8 (4)
0.015–0.25 (0.12) 0.008−0.5 (0.25)
0.12−8 (4)
0.03−0.5 (0.25)
0.12−1 (0.5)
0.00025–0.004 (0.004) 0.015−0.5 (0.25) 0.004−1 (na)
0.03−0.5 (0.25) 0.0005–0.004 (0.004) 0.015−0.5 (0.25) 0.004−1 (na)
0.004−2 (1)
0.004−2 (1)
a na, MIC 90 was not calculated for groups containing less than 10 isolates; P80: polysorbate 80.
Results: P80 reduced ORI MIC90 s by 16- to 32-fold for enterococci and staphylococci. In contrast, TEI and VAN MIC90 s were identical (the same or within one doubling dilution) with and without P80 with the exception of a 4-fold reduced TEI MIC90 for Ef with P80. P80 did not change MIC90 s for any agent against streptococci grown in cationadjusted Mueller-Hinton broth containing 2% lysed horse blood (LHB). Conclusions: Significant (16- to 32-fold) reductions in ORI MIC90 s were observed for enterococci and staphylococci with P80. A modest (4-fold) reduction in TEI MIC90 was observed for Ef +P80. ORI MICs ± P80 for streptococci were identical in the CLSI-recommended medium which contains LHB. Companion binding studies promote the idea that LHB may substitute for P80, which may help to explain the observed lack of shift in ORI MICs with P80 for streptococci. P828 Activity of daptomycin against coryneform bacteria isolated from clinical samples C. Salas, J. Calvo, L. Mart´ınez-Mart´ınez (Santander, ES) Objectives: To evaluate the activity of Daptomycin (DAP) and six other agents against coryneform bacteria of clinical origin. Methods: We evaluated 179 clinical isolates (1 per patient) including Corynebacterium striatum [Cstr (58)], C. amycolatum [Camy (25)], C. jeikeium [Cjei (25)], C. pseudodiphtheriticum [Cpse (21)], Listeria monocytogenes [Lmon (24)] and Arcanobacterium haemolyticum [Ahae (26)]. A microdilution assay, according to CLSI guidelines (M45-P), was used. The following antimicrobials were included: Clindamycin (CLI), Vancomycin (VAN), Teicoplanin (TEC), Linezolid (LNZ) and Quinupristin-dalfopristin (QDA). For DAP, Mueller-Hinton broth with 3% laked horse blood was supplemented with 50 mg/L of Ca++. S. pneumoniae ATCC 49619, S. aureus ATCC 29213 and E. faecalis ATCC 29212 were used as reference control strains. Results: MICs 50/90 (mg/L) values are presented in table 1. Table 1 Antimicrobial
CLI VAN TEC LNZ QDA DP
MIC50 /MIC90 Cstr
Camy
Cjei
Cpse
Lmon
Ahae
32/>32 0.25/0.5 0.06/0.12 0.25/0.5 0.12/0.5 0.06/0.5
>32/>32 0.25/0.5 0.12/0.25 0.12/0.25 0.06/0.25 0.06/0.06
>32/>32 0.06/0.25 0.06/0.12 0.25/0.5 0.25/1 0.25/0.25
>32/>32 0.25/0.25 0.06/0.25 0.25/0.5 0.06/0.06 0.06/0.06
0.5/1 0.5/1 0.06/0.25 2/4 0.5/1 2/4
0.015/0.015 0.25/0.5 0.06/0.06 0.25/0.5 0.06/0.06 0.5/0.5
Conclusions: Daptomycin has a good in vitro activity against C. striatum, C. amycolatum, C. jeikeium, C. pseudodiphtheriticum and A. haemolyticum, and presented reduced activity against L. monocytogenes. Teicoplanin, Vancomycin, Linezolid and Quinupristin-dalfopristin are also active against these organisms. Clindamycin was poorly active, in vitro, except against A. haemolyticum and L. monocytogenes.
17th ECCMID / 25th ICC, Posters
bactericidal lipoglycopeptide, has recently completed two Phase 3 clinical trials for the treatment of complicated skin and skin structure infections. Ongoing trials are assessing TLV for the treatment of hospitalacquired pneumonia. Because TLV will be used in the hospital setting, profiling its activity against enterococci is important. Methods: A total of 434 Enterococcus faecalis (EF) and 348 E. faecium (EM) isolates were collected from Europe (35 hospital sites in 14 countries) during 2004–2005. Isolates were centrally tested by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) methodology (M7-A7) against TLV and comparators. Results were analysed according to blood and non-blood specimen sources (SPECs). Results: The vancomycin-nonsusceptible (VAN-NS) rate for all EF was 5.5% and the VAN-NS rate for EM was 22.7%. The activity of TLV against the EF and EM isolates is shown in the Table. Conclusion: TLV demonstrated potent activity against all EF and EM isolates, regardless of SPEC. Based on MIC90 values, TLV was 16-fold more potent against vancomycin-susceptible (VAN-S) isolates compared with VAN-NS isolates among EF and EM. This evaluation of TLV activity will provide a baseline for comparison of in vitro activity as clinical development and use continues. Activity of telavancin against Enterococcus faecalis (EF) and E. faecium (EM) isolates Organism
Specimen
Phenotypea
source EF
Blood
Non-blood
EM
Blood
Non-blood
a VAN-S/VAN-NS,
All VAN-S VAN-NS All VAN-S VAN-NS All VAN-S VAN-NS All VAN-S VAN-NS
No. of
MIC (mg/L)
isolates
Range
MIC90
181 164 17 253 246 7 144 100 44 204 169 35
0.06−8 0.06−2 4−8 0.06−8 0.06−8 0.5−8 0.03−8 0.03−2 0.12−8 0.03−8 0.03−2 0.12−8
1 0.5 8 0.5 0.5 8 4 0.25 4 2 0.25 4
vancomycin-susceptible/nonsusceptible.
P827 Influence of polysorbate 80 on susceptibility of Gram-positive bacteria to oritavancin F.F. Arhin, I. Sarmiento, A. Belley, G. McKay, D. Draghi, P. Grover, D. Sahm, T.J. Parr Jr., G. Moeck (Saint Laurent, CA; Herndon, US) Objectives: Oritavancin (ORI) is a lipoglycopeptide (LG) with activity against Gram-positive bacteria. Broth microdilution (BMD) assays with dalbavancin, another LG, require 0.002% polysorbate 80 (P80). Following initial observations that P80 reduced ORI BMD minimum inhibitory concentrations (MICs) for reference strains of Staphylococcus aureus (Sa) ATCC 29213 and Enterococcus faecalis (Ef) ATCC 29212 but not for Streptococcus pneumoniae (Sp) ATCC 49619, we examined the effect of P80 on ORI MICs for 301 clinical isolates of these three genera. Methods: BMD assays were conducted on clinical isolates of Sa (n = 76), coagulase-negative staphylococci (CNS; n = 26), Ef (n = 70), E. faecium (Em; n = 30), Sp (n = 19), S. agalactiae (n = 29), S. pyogenes (n = 29), Groups C and G streptococci (n = 8), and Viridans Group streptococci (n = 14), either following CLSI guidelines (no P80) or with P80, in parallel. When tested in the presence of P80, ORI, vancomycin (VAN) and teicoplanin (TEI) were dissolved in 0.002% P80 and maintained in 0.002% P80 thereafter. Reference strains of Sa, Ef and Sp were tested concurrently.
MIC range (MIC 90a ), mg/L
Enterococci E. faecalis (n = 70) E. faecium (n = 30) Staphylococci S. aureus (n = 76) CNS (n = 26) Streptococci S. agalactiae (n = 29) S. pneumoniae (n = 19) S. pyogenes (n = 29) Group C and G (n = 8) Viridans group (n = 14)
ORI
ORI+P80
TEI
TEI+P80
VAN
VAN+P80
0.12−4 (2)
0.008−0.5 (0.12) 0.004−0.5 (0.25)
0.06−64 (0.5) 0.12–256 (64)
0.06−64 (0.12) 0.06–128 (128)
0.12–>256 (2) 0.25–>256 (>256)
0.5–>256 (2) 0.25–>256 (>256)
0.5−1 (1)
0.5−16 (1)
0.12−4 (2)
0.12−2 (0.5) 0.06−4 (2)
0.5−2 (1)
0.5−2 (2)
0.03–0.12 (0.06) 0.015–0.06 (0.06) 0.001–0.25 (0.06) 0.03–0.06 (na) 0.002–0.12 (0.06)
0.03–0.12 (0.06) 0.015–0.06 (0.06) 0.015–0.06 (0.03) 0.03–0.06 (na) 0.002–0.25 (0.12)
0.25−0.5 (0.5) 0.12−0.5 (0.25) 0.25−0.5 (0.25) 0.25−0.5 (na) 0.25−1 (0.5)
0.25−0.5 (0.5) 0.12−0.5 (0.25) 0.25−0.5 (0.25) 0.25−0.5 (na) 0.25−0.5 (0.5)
0.12−4 (4)
1−8 (4)
0.015–0.25 (0.12) 0.008−0.5 (0.25)
0.12−8 (4)
0.03−0.5 (0.25)
0.12−1 (0.5)
0.00025–0.004 (0.004) 0.015−0.5 (0.25) 0.004−1 (na)
0.03−0.5 (0.25) 0.0005–0.004 (0.004) 0.015−0.5 (0.25) 0.004−1 (na)
0.004−2 (1)
0.004−2 (1)
a na, MIC 90 was not calculated for groups containing less than 10 isolates; P80: polysorbate 80.
Results: P80 reduced ORI MIC90 s by 16- to 32-fold for enterococci and staphylococci. In contrast, TEI and VAN MIC90 s were identical (the same or within one doubling dilution) with and without P80 with the exception of a 4-fold reduced TEI MIC90 for Ef with P80. P80 did not change MIC90 s for any agent against streptococci grown in cationadjusted Mueller-Hinton broth containing 2% lysed horse blood (LHB). Conclusions: Significant (16- to 32-fold) reductions in ORI MIC90 s were observed for enterococci and staphylococci with P80. A modest (4-fold) reduction in TEI MIC90 was observed for Ef +P80. ORI MICs ± P80 for streptococci were identical in the CLSI-recommended medium which contains LHB. Companion binding studies promote the idea that LHB may substitute for P80, which may help to explain the observed lack of shift in ORI MICs with P80 for streptococci. P828 Activity of daptomycin against coryneform bacteria isolated from clinical samples C. Salas, J. Calvo, L. Mart´ınez-Mart´ınez (Santander, ES) Objectives: To evaluate the activity of Daptomycin (DAP) and six other agents against coryneform bacteria of clinical origin. Methods: We evaluated 179 clinical isolates (1 per patient) including Corynebacterium striatum [Cstr (58)], C. amycolatum [Camy (25)], C. jeikeium [Cjei (25)], C. pseudodiphtheriticum [Cpse (21)], Listeria monocytogenes [Lmon (24)] and Arcanobacterium haemolyticum [Ahae (26)]. A microdilution assay, according to CLSI guidelines (M45-P), was used. The following antimicrobials were included: Clindamycin (CLI), Vancomycin (VAN), Teicoplanin (TEC), Linezolid (LNZ) and Quinupristin-dalfopristin (QDA). For DAP, Mueller-Hinton broth with 3% laked horse blood was supplemented with 50 mg/L of Ca++. S. pneumoniae ATCC 49619, S. aureus ATCC 29213 and E. faecalis ATCC 29212 were used as reference control strains. Results: MICs 50/90 (mg/L) values are presented in table 1. Table 1 Antimicrobial
CLI VAN TEC LNZ QDA DP
MIC50 /MIC90 Cstr
Camy
Cjei
Cpse
Lmon
Ahae
32/>32 0.25/0.5 0.06/0.12 0.25/0.5 0.12/0.5 0.06/0.5
>32/>32 0.25/0.5 0.12/0.25 0.12/0.25 0.06/0.25 0.06/0.06
>32/>32 0.06/0.25 0.06/0.12 0.25/0.5 0.25/1 0.25/0.25
>32/>32 0.25/0.25 0.06/0.25 0.25/0.5 0.06/0.06 0.06/0.06
0.5/1 0.5/1 0.06/0.25 2/4 0.5/1 2/4
0.015/0.015 0.25/0.5 0.06/0.06 0.25/0.5 0.06/0.06 0.5/0.5
Conclusions: Daptomycin has a good in vitro activity against C. striatum, C. amycolatum, C. jeikeium, C. pseudodiphtheriticum and A. haemolyticum, and presented reduced activity against L. monocytogenes. Teicoplanin, Vancomycin, Linezolid and Quinupristin-dalfopristin are also active against these organisms. Clindamycin was poorly active, in vitro, except against A. haemolyticum and L. monocytogenes.