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Influence of polysorbate 80 on susceptibility of Gram-positive bacteria to oritavancin

Abstract number: 1733_325

Arhin F.F., Sarmiento I., Belley A., McKay G., Draghi D., Grover P., Sahm D., Parr Jr T.J., Moeck G.

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
ORIORI+P80TEITEI+P80VANVAN+P80  
Enterococci
E. faecalis (n = 70)0.12–4 (2)0.008–0.5 (0.12)0.06–64 (0.5)0.06–64 (0.12)0.12–>256 (2)0.5–>256 (2)
E. faecium (n = 30)0.12–4 (4)0.004–0.5 (0.25)0.12–256 (64)0.06–128 (128)0.25–>256 (>256)0.25–>256 (>256)
Staphylococci
S. aureus (n = 76)1–8 (4)0.015–0.25 (0.12)0.12–1 (0.5)0.12–2 (0.5)0.5–1 (1)0.5–16 (1)
CNS (n = 26)0.12–8 (4)0.008–0.5 (0.25)0.12–4 (2)0.06–4 (2)0.5–2 (1)0.5–2 (2)
Streptococci
S. agalactiae (n = 29)0.03–0.5 (0.25)0.03–0.5 (0.25)0.03–0.12 (0.06)0.03–0.12 (0.06)0.25–0.5 (0.5)0.25–0.5 (0.5)
S. pneumoniae (n = 19)0.00025–0.004 (0.004)0.0005–0.004 (0.004)0.015–0.06 (0.06)0.015–0.06 (0.06)0.12–0.5 (0.25)0.12–0.5 (0.25)
S. pyogenes (n = 29)0.015–0.5 (0.25)0.015–0.5 (0.25)<=0.001–0.25 (0.06)0.015–0.06 (0.03)0.25–0.5 (0.25)0.25–0.5 (0.25)
Group C and G (n = 8)0.004–1 (na)0.004–1 (na)0.03–0.06 (na)0.03–0.06 (na)0.25–0.5 (na)0.25–0.5 (na)
Viridans group (n = 14)0.004–2 (1)0.004–2 (1)0.002–0.12 (0.06)0.002–0.25 (0.12)0.25–1 (0.5)0.25–0.5 (0.5)
ana, MIC 90 was not calculated for groups containing less than 10 isolates; P80: polysorbate 80.

Results: P80 reduced ORI MIC90s by 16- to 32-fold for enterococci and staphylococci. In contrast, TEI and VAN MIC90s 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 MIC90s for any agent against streptococci grown in cation-adjusted Mueller-Hinton broth containing 2% lysed horse blood (LHB).

Conclusions: Significant (16- to 32-fold) reductions in ORI MIC90s 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.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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