Prediction and significance of synergy between antibiotics used for treatment for gram-negative sepsis.

Clinical tests capable of predicting synergism between penicillins and aminoglycosides are discussed. The results obtained in these tests are correlated to those of in vitro tests. Lack of in vitro synergism was associated with very low bactericidal activity in the serum. In order to determine the serum cidal activity tube dilutions were carried out using serum of plasma obtained from a patient who had received the antibiotic or a combination of drugs at a specified time before venipuncture. Dilutions were made with a pool of plasma or serum. This method needs further standardisation. It has been shown that the bactericidal dilutions of sera in patients treated with synergistic combinations were usually adequate, i. e. sera were active at a 1:8 dilution, while sera of most patients who received non-synergistic combinations were not active at this dilution. The determination of the bactericidal activity of the serum is not only a useful tool for monitoring therapy, it can be used also as an investigational means for comparing the respective efficacy of antibiotics administered alone or in combination. The test is probably more meaningful clinically than the simple in vitro microbiological studies or the determination of blood levels. It integrates some pharmacological characteristics of the drugs studied and the sensitivity of the pathogen to these drugs.