ANTIMICROBIAL AND ANTITUMOR ACTIVITIES 



85 



(Iroup 2 are a.s a rule neither antagonistic 

 nor synergistic to one another. When a 

 member of Group 1 is added to a member 

 of Group 2, the effect is unpredictable and 

 depends on the microorganism. 



^'arious methods of determining syner- 

 gism and antagonism among antibiotics 

 luu'e been proposed and were reviewed 

 briefly by Ghal)bert and Patte (1960), in a 

 paper in which they described a method 

 permitting the study of the bactericidal 

 synergistic effect of mixtures of antibiotics. 



Actinomycetes have been found to pro- 

 duce mixtures of antibiotics which are syn- 

 ergistic. For example, antibiotics PA 114A 

 and B are moi'e active in combination than 

 when used alone. 



Geminimycin is the j^erfect example of 

 such synei-gistic antibiotic pairs (Rao e( al., 

 1960). It is formed of two compounds, A 

 and B, which are antibiotically inactive. 

 The mixture A + B is active against gram- 

 positive bacteria. 



Antifungal Activities of Antibiotics 



It has been pointed out elsewhere that 

 actinomjTete antibiotics active upon fungi, 

 beginning with cycloheximide and ending 

 with many of the polyenes, have either no 

 activity at all or only very limited activity 

 upon bacteria. These anti})iotics are fre- 

 (juentl}' spoken of as antimycotics. Different 

 fungi, often strahis of the same species, differ 

 greath' in their sensiti\'ity to these agents. 

 Trichophijion mcntagrophytes and Candida 

 albicans are commonly used as test organ- 

 isms, with the agar-cup method. Bergman 

 (1955) suggested use of conidia only, a 

 conidial "bank" being recommended for this 

 purpose. Alcohol is usualh^ used as the 

 solvent, since most of the agents are not 

 soluble in water. Sabouraud's agar is com- 

 monly employed. 



A comparative study of the effect of 

 nystatin, amphotericin B, and candidin on 



Table 35 



Grouping of antibiotics on the basis of (heir activity 



against staphylococci (Waisbren and 



Strelitzer, 1960) 



Drug 



Neomycin 



Kanamycin 



Paromomycin . . 



Novobiocin 



Vancomycin 



Ristocetin 



Nitrofurantoin. . . 

 Oleandomycin. 

 Erythromycin. . 

 Streptomycin . . 



Tetracycline 



Oxytetracycline. . 



Penicillin 



Polymyxin B 



Bacitracin 



Chlortetracycline 

 Chloramphenicol . 



Group" 



Minima] inlii- 

 bitory con- 

 centration 

 (interpolated 

 from means 

 of inhibitory 

 tube) 



fig/ml 



0.35 



0.36 



0.41 



0.51 



0.86 



1.40 



5.79 



5.40 



5.43 



7.62 



7.20 



8.40 



11.46 



11.10 



11.70 



14.52 



21.60 



Per cent of 

 strains sus- 

 ceptible to 6 

 lig/ml or less 

 of the agent 

 (Abboud and 

 Waisbren, 

 1959) 



100 

 100 

 100 



96 

 100 

 100 



84 



73 



59 



59 



43 1 



40 



47t 



40 



35 



35 



15 



* Significant difTerence.s among members of the 

 groups were determined by analyzing the differ- 

 ence of the means of the number of tube dilutions 

 necessary for inhibition of the 75 strains of stai)h- 

 ylococci. The following formula was used: 



T = 



D 



VNiSi^ + N.,So2 



VNiN2(Ni + Na - 2) 

 N, + N, 



Antibiotics were considered to be significantly 

 different in activity if the P value of the difference 

 of means was <0.01; i.e., if there was less than 

 one chance in 100 that the means of the number 

 of tubes necessary for inhibition with each anti- 

 liiotic belonged in the same distribution and were 

 not representatives of different distributions. 

 The tubes were numbered as follows: > minimal 

 inhibitory concentration OlOO) = 11; 100 = 10; 

 50 = 9; 25 = 8; 12 = 7; 6 = 6; 3 = 5; 1.5 = 4; 

 0.75 = 3; 0.38 = 2; <0.38 = 1. 



t This means that a slightly greater percentage 

 of strains may be clinically susceptible to peni- 

 cillin, but that over-all tetracycline is moi-e ac- 

 tive on a weight for weight basis. 



