Antibiotic combinations: should they be tested?

Abstract

When antibiotic combinations are used to provide a broader spectrum of antimicrobial activity or in an attempt to prevent the emergence of resistant organisms, it is rarely necessary or practical to perform tests of drug interactions in vitro. In vitro testing of combinations may be useful when combinations are used in an attempt to attain synergistic interactions. In some cases, screening methods can be used as substitutes for formal synergy testing. This paper examines the mechanisms of antibiotic interaction leading to synergism or antagonism, surveys attempts to correlate in vitro observations with efficacy in animal models, and reviews clinical data providing evidence for or against a useful role of synergistic antibiotic interactions in the treatment of human infections.

Evaluation of the best method to assess antibiotic potentiation by phytochemicals against Staphylococcus aureus

“…It is not new that experimentation on drug interactions can lead to opposite conclusions by different methodologies. The various tests used measure quite distinct effects of antibiotic interactions against bacteria and use different endpoints (inhibition or killing) and medium state (broth versus agar) (Bonapace et al, 2000;Eliopoulos and Eliopoulos, 1988;White et al, 1996). However, with this strategy, it was obtained a good agreement between checkerboard, Etest, and DDM (77.5%).…”

“…This approach is based on some synergistic definitions applied for combinations involving 2 antimicrobials using checker-board (Mackay et al, 2000;Rand et al, 1996), Etest (Cantón et al, 2005;Lewis et al, 2002;Sopirala et al, 2010) and time-kill assay (Eliopoulos and Eliopoulos, 1988;NCCLS/CLSI, 1999). Table 1 presents the scheme proposed to classify an interaction as negative, indifferent, additive, or potentiation.…”

Versatility of Aminoglycosides and Prospects for Their Future

“…The issue of synergism against other microorganisms is less clear. Despite the fact that such a synergistic effect was also demonstrated for some strains of Enterobacteriaceae (80,148,219), Pseudomonas aeruginosa (29,56,147,209), staphylococci (33,34,252,310), including methicillin-resistant Staphylococcus aureus (MRSA) (125), and other microorganisms (80), many of these microorganisms were not inhibited by a combination of aminoglycoside and cell wall-active compounds (131,153,245). In a disconcerting development, antagonism between aminoglycosides and ␤-lactams was recently described (135).…”

The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans

“…The control contained fungal cells and broth medium with no drug. According to the previous report, synergism was defined as an increase of no less than 100-fold in killing for the combined agents compared with the most active agent used alone at 48 h, and antagonism was defined as a decrease of no less than 100-fold in killing for the combined agents compared with the most active agent alone at 48 h. Less than 100-fold in killing for the combined agents compared with any agents used was considered as indifference (Eliopoulos and Eliopoulos 1988).…”