Antagonistic antimicrobial combinations

The use of an antagonistic antimicrobial combination does not preclude other potential beneficial interactions. For example, rifampin may antagonize the action of anti-staphylococcal penicillins or vancomycin against staphylococci. However, the aforementioned antimicrobials may prevent the emergence of resistance to rifampin. 

Some combinations of antimicrobials are potentially antagonistic. For example, agents that are capable of inducing /1-lactamase production in bacteria (such as cefoxitin) may antagonize the effects of enzyme-labile drugs such as penicillins or imipenem. 

Co-trimoxazole consists of trimethoprim and sulphamethoxazole combined because of their synergistic antimicrobial effects. Trimethoprim is a folate antagonist that poses a teratogenic risk. 

Synergy studies are in vitro tests that attempt to measure synergistic, additive, indifferent, or antagonistic drug interactions. In general, these tests have not been standardized and have not correlated well with clinical outcome. (See section on Antimicrobial Drug Combinations for details.)... 

Fig. 11.7 Diagrammatic representation of MIC values obtained with two synergistic antimicrobials, penicillin and gentamicin. The resulting graph or isobologram (A) is obtained by linking MIC values for each drug alone and in various dilution combinations. The MIC values for penicillin and gentamicin alone are 1.0 mg/L and 32 mg/L, respectively. The slope of the isobologram for purely additive or antagonistic combinations is shown by B and C, respectively.

A number of studies have unequivocally demonstrated that anti-secretory/anti-biotic drug combinations including a PPI rather than an H2 receptor antagonist provide better eradication of H. pylori. Furthermore, the combination of a PPI and one or two antibiotic agent achieves H. pylori eradication rates indistinguishable from those found using bismuth triple therapy. Such studies have also noted an acceleration in rapid ulcer healing, less antimicrobial... 

---