Antibiotic Susceptibility Testing with Cubicin (daptomycin)

AnTIbIoTIC SuSCEpTIbIlITy TESTIng wITh CubICIn (daptomycin)

Introduction
Cubicin (daptomycin) is a cyclic lipopeptide antibiotic against Gram-positive bacteria, approved in Europe initially for complicated skin and soft tissue infections (cSSTIs)1 The label has recently been expanded to include: In Europe, Staphyococcus aureus bacteraemia when associated with right-sided infective endocarditis or cSSTI, and right-sided infective endocarditis due to S. aureus1 Daptomycin has one characteristic that affects susceptibility testing: It requires appropriate concentrations of free Ca2+ ions for accurate assessment of its activity in vitro24

Effect of Ca2+ on susceptibility testing

Daptomycin activity is dependent on the presence of physiological Ca2+ concentrations24 Other divalent and monovalent cations have negligible effects on activity2,5,6 A Ca2+ concentration of 50 g/ml (1.1 mM) in growth media provides optimal determination of daptomycin minimum inhibitory concentration (MIC) and correlates with physiological levels of free Ca2+ in human plasma (1.151.31 mM)7,8 Therefore, reliable in vitro susceptibility testing of daptomycin in clinical laboratories requires appropriate standardization of test media to 50 g/ml Ca2+

Summary of daptomycin susceptibility testing methods

Recommended methods for daptomycin susceptibility testing broth microdilution (bMD) The BMD is the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommended method for determining MIC and susceptibility of pathogens to daptomycin Follow CLSI-approved method using MuellerHinton broth (with or without 25% lysed horse blood) adjusted to 50 g/ml Ca2+ MIC determination using broths other than MuellerHinton broth has not been validated Etest* Daptomycin Etest strips (AB Biodisk, Sweden), which contain a constant Ca2+ level throughout the daptomycin gradient, are also a recommended method Ca2+ content in the agar is also essential and should be in the range of 2530 g/ml The daptomycin Etest strips are suitable for use on MuellerHinton agar (BBL MuellerHinton agar is recommended because the Ca2+ concentration is consistently within the required range)9 Automated and semi-automated systems Automated and semi-automated systems Development of daptomycin panels and cards for bioMerieux VITEK 1 and VITEK 2; BD Phoenix and Trek SensiTitre is complete Contact your local representative/customer services of the system manufacturer to obtain these systems and software updates as appropriate Other systems are in development non-recommended methods for susceptibility testing Agar dilution This method is not recommended because there is no agar with consistent Ca2+ concentrations that is also appropriate for daptomycin testing. Supplementing agar with Ca2+ is problematic The variability in Ca2+ concentrations of agar between different batches and manufacturers makes this method unpredictable Disk diffusion A 30 g disk was withdrawn from the US market due to problems in distinguishing resistant isolates from susceptible strains This method is currently not recommended

EuCAST-approved interpretive criteria10, (www.escmid.org)

Susceptible Staphylococcus spp. Streptococcus spp. Groups A, B, C and G (excluding S. pneumoniae)
*For further information and local distributor contact details go to www.abbiodisk.com. interpretive criteria for enterococci have not been set because there is insufficient clinical evidence for efficacy of daptomycin against these pathogens. interpretive criteria for S. pneumoniae have not been set because daptomycin is not indicated for community-acquired pneumonia.

Resistant >1 g/ml >1 g/ml

1 g/ml 1 g/ml

Susceptibility to Cubicin
Of 5,896 European Gram-positive clinical isolates tested by reference susceptibility methods in a 2008 European surveillance programme, 99.97% were susceptible to Cubicin11

Further information

Please contact your local Novartis office (see www.novartis.com)

References

1. Cubicin EU SmPC. 2. Eliopoulos GM et al. In vitro and in vivo activity of LY 146032, a new cyclic lipopeptide antibiotic. Antimicrob Agents Chemother 1986;30:532535. 3. Fuchs PC et al. Daptomycin susceptibility tests: interpretive criteria, quality control, and effect of calcium on in vitro tests. Diagn Microbiol Infect Dis 2000;38:5158. 4. Fuchs PC et al. Evaluation of daptomycin susceptibility testing by Etest and the effect of different batches of media. J Antimicrob Chemother 2001;48:557561. 5. Alborn WE Jr et al. Daptomycin disrupts membrane potential in growing Staphylococcus aureus. Antimicrob Agents Chemother 1991;35:22822287. 6. Eliopoulos et al. In vitro activity and mechanism of action of A21978C1, a novel cyclic lipopeptide antibiotic. Antimicrob Agents Chemother 1985;27:357362.
Cubicin (daptomycin) ABBREVIATED PRESCRIBING INFORMATION (powder for concentrate for solution for infusion). Refer to Summary of Product Characteristics (SmPC) before prescribing. orem ipsum dolor sit amet, consectetur adipiscing elit. Nunc ante nunc, dignissim ac vestibulum sit amet, viverra eget felis. Donec dapibus tristique aliquam. Morbi blandit facilisis risus, tristique semper dui sollicitudin vitae. Donec sodales nisi sed nunc adipiscing eu pretium magna commodo. Donec placerat auctor diam ut sollicitudin. Nam lacus ante, viverra vel lacinia non, hendrerit sit amet quam. Pellentesque id arcu ligula, eget commodo tellus. Mauris viverra laoreet nulla, sed placerat lacus hendrerit id. Quisque mauris felis, egestas in mollis ac, iaculis vel justo. Donec luctus ipsum id diam molestie ut tempus justo egestas. Suspendisse pulvinar commodo felis, vitae dignissim tellus laoreet eget. Donec tincidunt auctor faucibus. Sed mattis bibendum tincidunt. Duis est odio, eleifend ac sagittis non, tincidunt eu est. Vivamus at elit nulla. Duis ultrices mattis suscipit. Duis sem augue, porttitor et mollis sit amet, mattis ac nulla. Praesent feugiat semper est, facilisis ullamcorper nulla laoreet eget. Curabitur auctor pretium orci vel porttitor.Sed dapibus imperdiet venenatis. Maecenas elit orci, lobortis nec ullamcorper pellentesque, lacinia ut ipsum. Ut lacinia dui a eros consectetur dignissim. Vestibulum eleifend augue sed libero placerat eget pulvinar nisi suscipit. Cras gravida condimentum massa, non aliquet nulla ullamcorper pretium. Sed rhoncus dictum justo ut pretium. Vestibulum iaculis lectus vitae orci aliquam fermentum. Maecenas venenatis, velit nec vestibulum accumsan, eros dolor eleifend mi, non pulvinar lorem urna at diam. Pellentesque adipiscing consequat tristique. Maecenas aliquam gravida augue ut elementum. In non purus eu erat faucibus fringilla. Fusce pharetra venenatis vestibulum. Praesent quis sagittis neque. In dignissim, quam et scelerisque tincidunt, risus augue bibendum eros, non luctus sem dui sed turpis.Fusce quis imperdiet augue. Pellentesque posuere pellentesque lorem eu cursus. Donec lacinia purus sed nunc porttitor quis fringilla lacus bibendum. Nulla rutrum nisl ut arcu molestie ut semper mauris venenatis. Proin eleifend turpis eu massa scelerisque sollicitudin. Duis nunc ligula, congue dictum rutrum non, commodo ut arcu. Proin porttitor lacinia varius. Nunc sollicitudin justo rhoncus nibh porttitor sed iaculis est molestie. Sed metus purus, hendrerit vitae consequat in, suscipit sit amet velit. Pellentesque lobortis facilisis ante, non pulvinar sapien pulvinar sit amet. Fusce sodales hendrerit turpis a molestie. In ac est et eros venenatis bibendum. Sed fermentum mattis lectus, ut fringilla justo euismod et. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Pellentesque dictum rhoncus odio, vel gravida dolor consectetur vitae. Aenean pharetra nulla a odio tincidunt pulvinar. Morbi euismod arcu nec arcu molestie feugiat. Donec in dui arcu.Sed blandit commodo dui eu euismod. Fusce blandit laoreet congue. Ut felis eros, varius non euismod eu, eleifend in nisi. Suspendisse mauris urna, pulvinar nec facilisis commodo, sagittis placerat nisi. Nullam eget adipiscing nisl. Quisque ac lacus a nisl laoreet accumsan quis non magna. Nulla turpis turpis, pharetra sed tempor vel, tempus ornare quam. Pellentesque habitant morbi tristique senectus et netus et malesuada fames ac turpis egestas. Nulla augue ante, tincidunt ut posuere in, dictum id enim. Aliquam feugiat egestas vulputate. Cras pharetra velit lacinia erat elementum gravida. Sed in purus at arcu imperdiet congue. Vestibulum vel turpis nec nisi tempor semper vel nec ligula. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Vestibulum ante ipsum primis in faucibus orci luctus et ultrices posuere cubilia Curae;Maecenas feugiat mi at massa consectetur malesuada. Phasellus suscipit imperdiet lorem in hendrerit. Mauris ac metus tellus. Aliquam erat volutpat. Curabitur pharetra aliquam nisi sed euismod. Praesent congue venenatis diam, ultrices commodo lacus convallis vel. Morbi turpis sem, pellentesque in luctus ut, volutpat id arcu. Proin ac tempus magna. In hac habitasse platea dictumst. Suspendisse tristique justo blandit libero egestas vel consequat sapien posuere. Pellentesque habitant morbi tristique senectus et netus et malesuada fames ac turpis egestas.vestibulum sit amet, viverra eget felis. Donec dapibus tristique aliquam. Morbi blandit facilisis risus, tristique semper dui

7. Barry AL et al. In vitro activities of daptomycin against 2,789 clinical isolates from 11 North American medical centers. Antimicrob Agents Chemother 2001;45:19191922. 8. Wise R et al. Activity of daptomycin against Gram-positive pathogens: a comparison with other agents and the determination of a tentative breakpoint. J Antimicrob Chemother 2001;48:563567. 9. AB BIODISK. Etest daptomcyin product leaflet. 2007. 10. EUCAST. EUCAST Clinical MIC breakpointsdaptomycin. Available at: http://www.srga.org/eucastwt/mictab/micdaptomycin.html [accessed 8 April 2008]. 11. Sader HS et al. Antimicrobial Activity and Spectrum of Daptomycin. JMI Laboratories, Iowa; 2009

sollicitudin vitae. Donec sodales nisi sed nunc adipiscing eu pretium magna commodo. Donec placerat auctor diam ut sollicitudin. Nam lacus ante, viverra vel lacinia non, hendrerit sit amet quam. Pellentesque id arcu ligula, eget commodo tellus. Mauris viverra laoreet nulla, sed placerat lacus hendrerit id. Quisque mauris felis, egestas in mollis ac, iaculis vel justo. Donec luctus ipsum id diam molestie ut tempus justo egestas. Suspendisse pulvinar commodo felis, vitae dignissim tellus laoreet eget. Donec tincidunt auctor faucibus. Sed mattis bibendum tincidunt. Duis est odio, eleifend ac sagittis non, tincidunt eu est. Vivamus at elit nulla. Duis ultrices mattis suscipit. Duis sem augue, porttitor et mollis sit amet, mattis ac nulla. Praesent feugiat semper est, facilisis ullamcorper nulla laoreet eget. Curabitur auctor pretium orci vel porttitor.Sed dapibus imperdiet venenatis. Maecenas elit orci, lobortis nec ullamcorper pellentesque, lacinia ut ipsum. Ut lacinia dui a eros consectetur dignissim. Vestibulum eleifend augue sed libero placerat eget pulvinar nisi suscipit. Cras gravida condimentum massa, non aliquet nulla ullamcorper pretium. Sed rhoncus dictum justo ut pretium. Vestibulum iaculis lectus vitae orci aliquam fermentum. Maecenas venenatis, velit nec vestibulum accumsan, eros dolor eleifend mi, non pulvinar lorem urna at diam. Pellentesque adipiscing consequat tristique. Maecenas aliquam gravida augue ut elementum. In non purus eu erat faucibus fringilla. Fusce pharetra venenatis vestibulum. Praesent quis sagittis neque. In dignissim, quam et scelerisque tincidunt, risus augue bibendum eros, non luctus sem dui sed turpis.Fusce quis imperdiet augue. Pellentesque posuere pellentesque lorem eu cursus.Donec lacinia purus sed nunc porttitor quis fringilla lacus bibendum. Nulla rutrum nisl ut arcu molestie ut semper mauris venenatis. Proin eleifend turpis eu massa scelerisque sollicitudin. Duis nunc ligula, congue dictum rutrum non, commodo ut arcu. Proin porttitor lacinia varius. Nunc sollicitudin justo rhoncus nibh porttitor sed iaculis est molestie. Sed metus purus, hendrerit vitae consequat in, suscipit sit amet velit. Pellentesque lobortis facilisis ante, non pulvinar sapien pulvinar sit amet. Fusce sodales hendrerit turpis a molestie. In ac est et eros venenatis bibendum. Sed fermentum mattis lectus, ut fringilla justo euismod et. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Pellentesque dictum rhoncus odio, vel gravida dolor consectetur vitae. Aenean pharetra nulla a odio tincidunt pulvinar. Morbi euismod arcu nec arcu molestie feugiat. Donec in dui arcu.Sed blandit commodo dui eu euismod. Fusce blandit laoreet congue. Ut felis eros, varius non euismod eu, eleifend in nisi. Suspendisse mauris urna, pulvinar nec facilisis commodo, sagittis placerat nisi. Nullam eget adipiscing nisl. Quisque ac lacus a nisl laoreet accumsan quis non magna. Nulla turpis turpis, pharetra sed tempor vel, tempus ornare quam. Pellentesque habitant morbi tristique senectus et netus et malesuada fames ac turpis egestas. Nulla augue ante, tincidunt ut posuere in, dictum id enim. Aliquam feugiat egestas vulputate. Cras pharetra velit lacinia erat elementum gravida. Sed in purus at arcu imperdiet congue. Vestibulum vel turpis nec nisi tempor semper vel nec ligula. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Vestibulum ante ipsum primis in faucibus orci luctus et ultrices posuere cubilia Curae;Maecenas feugiat mi at massa consectetur malesuada. Phasellus suscipit imperdiet lorem in hendrerit. Mauris ac metus tellus. Aliquam erat volutpat. Curabitur pharetra aliquam nisi sed euismod. Praesent congue venenatis diam, ultrices commodo lacus convallis vel. Morbi turpis sem, pellentesque in luctus ut, volutpat id arcu. Proin ac tempus magna. In hac habitasse platea dictumst. Suspendisse tristique justo blandit libero egestas vel consequat sapien posuere. Pellentesque habitant morbi tristique senectus et netus et malesuada fames ac turpis egestas.vestibulum sit amet, viverra eget felis. Donec dapibus tristique aliquam. Morbi blandit facilisis risus, tristique semper dui sollicitudin vitae. Donec sodales nisi sed nunc adipiscing eu pretium magna commodo. Donec placerat auctor diam ut sollicitudin. Nam lacus ante, viverra vel lacinia non, hendrerit sit amet quam. Pellentesque id arcu ligula, eget commodo tellus. Mauris viverra laoreet nulla, sed placerat lacus hendrerit id. Quisque mauris felis, egestas in mollis ac, iaculis vel justo. Donec luctus ipsum id diam molestie ut tempus justo egestas. Suspendisse pulvinar commodo felis, vitae dignissim tellus