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10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Deutsche Gesellschaft für Infektiologie,
Deutsche AIDS-Gesellschaft,
Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit,
Paul-Ehrlich-Gesellschaft für Chemotherapie

23.06. - 26.06.2010, Köln

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In vitro activity of daptomycin combined with other antimicrobial agents against Gram-negative bacteria

In vitro Aktivität von Daptomycin in Kombination mit anderen Antibiotika gegenüber Gram-negativen Bakterien

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  • B. Körber-Irrgang - Antiinfectives-Intelligence GmbH, Rheinbach, Germany
  • M. Kresken - Antiinfectives-Intelligence GmbH, Rheinbach, Germany

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP10

doi: 10.3205/10kit066, urn:nbn:de:0183-10kit0660

Published: June 2, 2010

© 2010 Körber-Irrgang et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objectives: Daptomycin (DAP), a cyclic lipopeptide, exerts rapid bactericidal activity against clinically important gram-positive bacteria. Combination therapy might be beneficial to cover also gram-negative pathogens in mixed infections. We evaluated the in vitro activities of DAP in combination with 11 other relevant drugs against clinical isolates of Escherichia coli (ECO), Klebsiella pneumoniae (KPN), Klebsiella oxytoca (KOX), Enterobacter cloacae (ECL), Pseudomonas aeruginosa (PAE) and Acinetobacter baumannii (ABA).

Methods: A total of 50 organisms including strains with various resistance phenotypes were studied. Synergy testing was performed by using the checkerboard broth microdilution method. DAP in combination with amikacin (AMK), tobramycin (TOB), ceftazidime (CAZ), ceftriaxone (CRO), piperacillin-tazobactam (P/T), meropenem (MEM), imipenem (IMP), ciprofloxacin (CIP), moxifloxacin (MOX) or fosfomycin (FOS) were tested against strains of ECO (n=10), ECL (n=10), KPN (n=6) and KOX (n=4) (in total 300 drug combination tests), while DAP in combination with AMK, TOB, CAZ, P/T, MEM, IMP, CIP, MOX or colistin (COL) was tested against 10 strains each of PAE and ABA (in total 180 drug combination tests). The fractional inhibitory concentration indices (FICIs) were calculated to interpret the results. Synergism was defined as FICI ≤0.5, indifference as FICI >0.5 to ≤4, and antagonism as FICI >4.

Results: Antagonism was not detected with any combination. Of the 300 drug tests performed with the enterobacterial strains, 284 revealed an indifferent effect, while synergism of DAP plus CIP, CRO, MEM or MOX was observed for 10, 3, 2 and 1 strain, respectively. For non-fermenting bacteria indifference was observed for nearly all drug combinations, while synergism was seen for 2 ABA with COL and 1 ABA with TOB.

Conclusions: DAP did not antagonise the activity of antibacterial agents directed to gram-negative bacteria and may thus be combined with these drugs for the treatment of bacterial mixed infections.